The present study was supported by grants from Kidney Research UK (ST4/2011), the Cunningham Trust (CT11/14), the Mrs AE Hogg Charitable Trust for Kidney Research and the Renal Endowment Fund of the Royal Infirmary of Edinburgh.

Genel Rehberlik: Hayvan deneyleri Hayvanlar dayattığı kurallara ve yönetmeliklere uygun (Bilimsel Prosedürler) Yasası 1986 Bu protokol ve çok sayıda yapılabilir eşlik eden video protokol standart UUO ve R-UUO hem içindir, yapılmıştır fare suşları. Eşlik eden video, hem prosedürler erkek C57BL / 6 fareler yaş 8 hafta yapılmaktadır. Örnek sonuçlar bölümünde sunulan veriler erkek FVB / N farelerden elde edilmiştir. NOT: Bu protokol ve nasıl bir standart UUO gerçekleştirmek ve R-UUO sol üreter kullanan video ayrıntılarını eşlik, ancak aynı teknikler kolayca sağ üreter uygulanabilir. 1. Hayvan Hazırlama ve laparotomi <ol><li> Steril (otoklav) araçların ve sarf malzemeleri ile tüm prosedürleri uygulayın. </li><li> Uyuşturmak için intraperitonal ketamin hidroklorür (70 mg / kg) ve medetomidin hidroklorür (1 mg / kg) enjekteFare. Not: Elde edilen anestezik düzlemin süresi 4 saat olan ve hiçbir ek anestezi gereklidir. </li><li> Refleksler, örneğin, ayak tutam kaybı ile anestezi derinliği onaylayın. </li><li> Kesi alanı çevreleyen tüm saç çıkarın ve bir seyreltik klorheksidin solüsyonu uygulaması yoluyla ameliyat için karın cildi hazırlar. </li><li> Sırtüstü pozisyonda ısıtılmış cerrahi pad üzerinde fare koyun ve düşük yapışma yapıştırıcı bant kullanarak pad bacaklarda düzeltmek. </li><li> İşlem sırasında, ısıtılmış ameliyat pedin bir sonucu olarak termal yanıklar belirtileri için fare izler. Mümkünse bir elektrikli olmayan ısı kaynağı kullanın. </li><li> Buprenorfin hidroklorür (0.06mg / kg) deri altından enjeksiyonu ile analjezik yönetme ve kornea kurumasını önlemek için göz yağ uygulanır. </li><li> Bir orta hat laparotomi ve periton boşluğuna erişmek için doku ayıran makas kullanarak avasküler linea alba bir kesi yapmak. </li><li> Fareyi asmak ve bir colibri eklemekkesi içine toplayıcı. </li></ol> 2. Tek taraflı Üreterik İkaz <ol><li> Sterilize pamuk tomurcukları kullanılarak karın boşluğunun sağ tarafına doğru bağırsakları yerinden bıraktığı üreter ortaya çıkarmak ve nemli örtüler ile bunları kapatın. </li><li> Açılı forseps izole ve sol üreter kaldırın kullanma. </li><li> Bir üreter tıkanıklığı oluşturmak için, her yerde mesane ve böbrek pelvis arasındaki 6 / Ç siyah örgü ipek sütür ile iki kez sol üreter Arter. Uzun süreli deneyler için, tüm karın ameliyatları için emilebilir sütür kullanın. Seçenek olarak ise, bir linear klip üreter uygulanabilir. </li><li> Üreter gelen mesane izole etmek için, iki sütür arasındaki üreter bölün. </li><li> Dikkatle periton boşluğuna bağırsak değiştirin. </li><li> Bölüm 4&#39;te listelenen adımları izleyin - Post-Operatif Kurtarma ve Bakım kesi kapatın ve anestezi ters. </li></ol> Reversibl 3. Hazırlıke Tek Taraflı Üreterik İkaz <ol><li> Ameliyat için fare hazırlayın ve Adımlar yukarıda 1,1-2,2 ayrıntılı olarak sol üreter izole. </li><li> Tersine bir üreter tıkanıklığı oluşturmak için, mesaneye yakın 6 / Ç siyah örgü ipek sütür ile iki kez sol üreter Arter. Bu üreter çevresinde yer yumuşak duvarlı plastik boru sabitlemek için kullanılacak uzun üst ameliyat dikiş ipliğinin bir ucu boş. </li><li> O üreter uygulanacak izin vermek için açık yayvan olabilir, öyle ki, yumuşak çeperli plastik bir boru 5 mm uzunluğunda, uzunlamasına bir yarık olun. 1 mm ve 2 mm dış çaplı bir iç çapa sahip herhangi bir yumuşak duvarlı silikon plastik boru, kullanılabilir. </li><li> Üreter etrafında yavaşça yumuşak duvarlı plastik boru yerleştirin. O üreter etrafında kapalı bir kez uzun dikiş boru yarık merkezinden çıkan emin olun. </li><li> Üreter çevreleyen yumuşak duvarlı boru yaklaşık 6 / Ç siyah örgülü ipek sütür uzunluğu yerleştirin ve kravatbir kez. Şimdi uzunlamasına bir önceki bağlı dikiş üstünde uzandığı şekilde boru boyunca, boru yarık merkezinden çıkan, ameliyat dikiş ipliğinin, uzun ucuna yerleştirin. </li><li> Boru ve üreter etrafında yerinde uzun dikiş ucunu tutturmak için iki kez tüp etrafında bulunan dikiş kravat. Not: üreter ve yumuşak duvarlı plastik boru üzerinde yapışma oluşumunu önlemek için, bir yapışma azaltma çözümü boru çevresi uygulanabilir. </li><li> Dikkatle periton boşluğuna bağırsak değiştirin. </li></ol> 4. Post-Operatif Kurtarma ve Bakım <ol><li> 5 / Ç siyah örgü ipek sütür kullanarak battaniye dikiş ile periton kapatın ve metalik deri klipleri kullanarak cilt yaklaşmaktadır. </li><li> Post-operatif enfeksiyon riskini en aza indirmek için, karın deriye iyot / alkol çözeltisi gibi bir antiseptik gibi uygulayın. </li><li> Subkutan atipamezol hidroklorür (2mg / kg) ile kısmen ters anestezi. </li&gt; <li> 1 ml &#39;lik bir deri altından enjeksiyon ile sıvıları yönetme tuz ısıtıldı. </li><li> Bu bilinci kurtarıldı kadar fare izleyin. </li><li> Fare, 24 saat için 29 ° C&#39;da tutulan bir ateşli kutusuna geri izin verin. Nemlendirilmiş Gıda da sıvı ve beslenme alımını teşvik sağlanabilir. </li><li> Tıkanma arzu edilen düzeyde bir, tipik olarak 7 gün uyarılması için geri fare bırakın. </li><li> Uzun vadeli iyileşme deneyleri için, devam eden analjezikler sağlanması. Fare daha uzun 7 gün süre ile, elde edilecek olan ise, cilt klipleri cerrahi sonrası 7 gün çıkarın. </li><li> Tıkanıklığı, istenen seviyede indüklenmiş sonra, ya da aşağıda tarif edildiği gibi, UUO ters ya da servikal bozma ile fare ötenazi ve histopatoloji analizi için böbrek toplar. </li></ol> 5. Döner Tek Taraflı Üreterik İkaz <ol><li> Adımlarda açıklandığı gibi R-UUO ameliyat öncesi, R UUO hazırlık görmüş bir fare hazırlamak gerçekleştirmek için 10,1-1,7. </li><li> Varsa, cilt klipleri kaldırmak ve bölmek veya karın boşluğuna erişmek için periton sütür kaldırın. Not: üreter uzun vadeli deney cilt klipleri için engel olmuşsa uygulama aşağıdaki 7 gün kaldırılmış olmalıdır. </li><li> Fareyi hazırlayın ve adımlar 1,8-2,2 açıklandığı gibi sol üreter izole. </li><li> Açılı forseps kullanarak, oluşmuş olabilecek granülomatöz doku yumuşak duvarlı plastik boru ücretsiz. </li><li> Bir neşter ile üreter etrafında plastik boru tutan dikiş kesin ve tüp çıkarın. </li><li> Sol böbrekte hidronefroz varlığı için değerlendirerek başarılı UUO onaylayın, böbrek de soluk görünmelidir. </li><li> Sütür arasındaki üreter bölün. </li><li> Steril gazlı bez küçük bir parçası üzerinde, böbrek bağlı üreter kalan uzunluğu, yerleştirin. Bu üreter a akacak idrar sediment ve ölü hücreleri toplamak için kullanılacaknd dikiş kez renal pelvis kaldırılır. </li><li> Yukarıdaki üreter bölün, ancak yakın, dikiş ve böbrek gazlı bez üzerine süzülmesini bekleyin. Mesaneye yakın, sağlam, düşük dikiş bırakın. Bu hiçbir idrar kesesinden ve periton boşluğuna sızıntı olmasını sağlamak için. </li><li> Üreter ve renal pelvis boşaldıktan sonra, üreter kalan uzunluğu sonuna uzun bir 6 / Ç siyah örgü ipek sütür uygulayın. Bu daha sonra yapılan mesane anastomoz üreter yardımcı olmak için kullanılır. </li><li> Mesane içine üreter kalan uzunluğunu anastomoz için aşağıdaki adımları izleyin: <ol><li> Bu orijinal konumuna anterior uzaklıkta ve böbrek üzerinde yer alır, öyle ki üreter getirin. </li><li> Mesane yönünde ortaya şekilde üreter sonunda tek bir 9 / Ç poliamid monofilament sütür teyel 2 mm yerleştirin. Dikiş kas kat kalır ve üreter lümeni girmemesini sağlamak için özen gösterin. teyel dikiş will mesane üreter sabitlemek için kullanılır. </li><li> Mesane ile kanal oluşturmak için, mesane ön (ventral) duvara doğru çıkar şekilde mesane ile çapraz bir 21G iğne geçmek. </li><li> 21G iğne konik bir gözlü iğne dinlendirin. Mesane yoluyla gözlü iğne rehberlik 21G iğne kullanın. gözlü iğne mesane ile üreter almak için kullanılacaktır. </li><li> 9 / Ç teyel dikiş geçmek, mesane ve dışarı giriş noktasına komşu mesane duvarı üzerinden ilk kesiden adım 5.11.2 yılında üreter başvurdu. Üreter mesane geçirilir sonra bu mesaneye üreter çapa bağlı olacaktır. </li><li> Gözlü iğne ile adım 5.10 üreter sonunda uygulanan uzun 6 / Ç siyah örgü ipek sütür yerleştirin. </li><li> Dikkatle üreter de mesane yoluyla çekilir sağlamak iken mesane dışına gözlü iğneyi çıkartın. </li><li> Üreter th çıkan keze mesane gözlü iğneyi çıkarın ve geri mesane içine geri çekilmesini önlemek için üreter sonunda uzun dikiş için bir kelepçe uygulayın. </li><li> Mesane yerde içinde üreter çapa, adım 5.11.5 uygulanan 9 / Ç poliamid monofilament tack dikiş, kravat. </li><li> Sıkıca mesane içinde üreter demirlemek için giriş noktası yaklaşık iki noktada adım 5.11.2 ve 5.11.5 açıklandığı gibi ek tek 9 / Ç poliamid monofilament sütür kravat uygulayın. </li><li> Açılan makas arka kullanarak, acil üreter daha ortaya çıkarmak için hafifçe geri mesane duvarı itin. </li><li> Üreter sonunda bulunan uzun dikiş üzerinde üreter bölün. Üreter mesane vücuda geri çekilmelidir. Bu üreter açık lümen teyit mesane açıklığından dışarı akan idrar gözlemlemek olağandır. </li><li> 9 / Ç poliamid monofilament sütür ile mesane yara çıkış kapatın. </li></ol></li><li> Dikkatle içine bağırsakları yerinePeriton boşluğu. </li><li> Adımlar 4,1-4,8 ayrıntılı olarak post-operatif bakım sağlayın. </li><li> Böbrek 7 gün tipik, sıkıştırılmış kadar fare kurtarmak için izin verin. </li><li> Deneysel son noktada, servikal dislokasyon ile fare euthanize ve histopatolojik analiz için böbrekleri toplamak. </li></ol>

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C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Postobstructive+regeneration+of+kidney+is+derailed+when+surge+in+renal+stem+cells+during+course+of+unilateral+ureteral+obstruction+is+halted.">Postobstructive regeneration of kidney is derailed when surge in renal stem cells during course of unilateral ureteral obstruction is halted.</a> Am J Physiol Renal Physiol. 298, F357-F364 (2010).</li><li>Manson, S. R., Niederhoff, R. A., Hruska, K. A., Austin, P. 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D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Contrasting+effects+of+systemic+monocyte/macrophage+and+CD4++T+cell+depletion+in+a+reversible+ureteral+obstruction+mouse+model+of+chronic+kidney+disease.">Contrasting effects of systemic monocyte/macrophage and CD4+ T cell depletion in a reversible ureteral obstruction mouse model of chronic kidney disease.</a> Clin Dev Immunol. 2013, 836-989 (2013).</li><li>Haque, M. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Longitudinal+changes+in+MRI+markers+in+a+reversible+unilateral+ureteral+obstruction+mouse+model:+preliminary+experience.">Longitudinal changes in MRI markers in a reversible unilateral ureteral obstruction mouse model: preliminary experience.</a> J Magn Reson Imaging. 39, 835-841 (2014).</li><li>Bai, Z. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Arterially+transplanted+mesenchymal+stem+cells+in+a+mouse+reversible+unilateral+ureteral+obstruction+model:+in+vivo+bioluminescence+imaging+and+effects+on+renal+fibrosis.">Arterially transplanted mesenchymal stem cells in a mouse reversible unilateral ureteral obstruction model: in vivo bioluminescence imaging and effects on renal fibrosis.</a> Chinese Med J. 126, 1890-1894 (2013).</li><li>Chaabane, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Renal+functional+decline+and+glomerulotubular+injury+are+arrested+but+not+restored+by+release+of+unilateral+ureteral+obstruction+(UUO).">Renal functional decline and glomerulotubular injury are arrested but not restored by release of unilateral ureteral obstruction (UUO).</a> Am J Physiol Renal Physiol. 304, F432-F439 (2013).</li><li>Thornhill, B. A., Burt, L. E., Chen, C., Forbes, M. S., Chevalier, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Variable+chronic+partial+ureteral+obstruction+in+the+neonatal+rat:+a+new+model+of+ureteropelvic+junction+obstruction.">Variable chronic partial ureteral obstruction in the neonatal rat: a new model of ureteropelvic junction obstruction.</a> Kidney Int. 67, 42-52 (2005).</li><li>Thornhill, B. A., Chevalier, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Variable+partial+unilateral+ureteral+obstruction+and+its+release+in+the+neonatal+and+adult+mouse.">Variable partial unilateral ureteral obstruction and its release in the neonatal and adult mouse.</a> Methods Mol Biol. 886, 381-392 (2012).</li></ol>

Yazarlar hiçbir rakip ya da ifşa etmek çıkarları çatışan var.

Obstruction of the kidney may affect native or transplanted kidneys and results in kidney injury and scarring. The R-UUO model is of relevance to human disease as patients often present with obstruction of the renal tract secondary to prostatic hypertrophy, posterior urethral valves etc. that requires decompression with patients commonly left with significant residual kidney impairment that has no current treatment options and may eventually lead to end stage kidney disease.8,9 The models detailed here enable ...

The overall aim of the experimental model described here is to induce obstructive nephropathy by unilateral ureteric obstruction (UUO), which can either be irreversible (UUO) or reversible (R-UUO). A simple irreversible model of UUO is presented in which the left ureter is permanently obstructed by ligation with a suture or by the application of a ligating clip. This results in marked dilatation of the ureter together with reduced renal blood flow and glomerular filtration. Renal histology demonstrates tubular dilatation and increasingly severe interstitial renal inflammation and fibrosis. Irreversible UUO is a useful model and has been adopted by many researchers in the study of both renal inflammation and fibrosis.1-4 Although the irreversible model of UUO requires some surgical expertise it is relatively straightforward and is often used to seek insights into the pathogenesis of interstitial renal injury and the ensuing fibrosis. Also presented is a less frequently used R-UUO model using a modification of the method originally described by Tapmeier et al.5 The R-UUO model has much future potential for the study of inflammatory and immune processes, cellular and tissue regeneration as well as the subsequent tissue remodeling following the removal of an injurious stimulus. 
The more challenging R-UUO model has been used by a limited number of investigators with some groups employing a significantly different surgical technique to that described here6,7 though with interesting results. In the R-UUO model presented, the ureter is ligated to induce complete ureteric obstruction for a period of time sufficient to induce the level of injury and fibrosis desired: 7 days of UUO was chosen in the method described here. The ureteric obstruction is reversed and the kidney is allowed to decompress for a period of time determined by the investigator before the mice are culled and the kidney removed for analysis: 7 days of decompression was chosen in the method described here though a longer period would be chosen if the resolution of inflammation and fibrosis was being studied. Although the method described here requires significant surgical expertise, it offers several advantages over other R-UUO models. The application of soft walled plastic tubing to the obstructed ureter prevents excessive ureteric dilation and this facilitates the subsequent manipulation and anastomosis of the ureter. Furthermore, in the described R-UUO model the ureter is divided thereby allowing the removal of any residual urinary sediment and debris. This confirms that the remaining ureter lumen is de-obstructed and patent prior to anastomosis to the bladder. 
Experiments incorporating both the irreversible and reversible UUO models can provide researchers with a powerful insight into the molecular and cellular mechanisms of both injury and subsequent resolution and regeneration. Thus, the model of R-UUO described here would be highly relevant to researchers interested in post-inflammatory tissue remodeling and how this can be modulated.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Blunt Dissecting Scissors</td>
			<td>Fine Science Tools</td>
			<td>14072-10</td>
			<td></td>
		</tr>
		<tr>
			<td>Spring Scissors &#8211; straight</td>
			<td>Fine Science Tools</td>
			<td>15000-10</td>
			<td></td>
		</tr>
		<tr>
			<td>Toothed forceps</td>
			<td>Fine Science Tools</td>
			<td>11021-12</td>
			<td></td>
		</tr>
		<tr>
			<td>Angled forceps x 2</td>
			<td>Fine Science Tools</td>
			<td>00649-11</td>
			<td></td>
		</tr>
		<tr>
			<td>Straight forceps</td>
			<td>Fine Science Tools</td>
			<td>00632-11</td>
			<td></td>
		</tr>
		<tr>
			<td>Colibri 3cm wire retractor</td>
			<td>Fine Science Tools</td>
			<td>17000-03</td>
			<td></td>
		</tr>
		<tr>
			<td>Castroviejo needle holder with lock</td>
			<td>Fine Science Tools</td>
			<td>12565-14</td>
			<td></td>
		</tr>
		<tr>
			<td>Wound clip applicator</td>
			<td>Fine Science Tools</td>
			<td>12031-07</td>
			<td></td>
		</tr>
		<tr>
			<td>7mm wound clips</td>
			<td>Fine Science Tools</td>
			<td>12032-07</td>
			<td></td>
		</tr>
		<tr>
			<td>Castroviejo micro needle holder with lock</td>
			<td>Fine Science Tools</td>
			<td>12060-01</td>
			<td></td>
		</tr>
		<tr>
			<td>OPMI pico microscope</td>
			<td>Carl Zeiss</td>
			<td>S100</td>
			<td></td>
		</tr>
		<tr>
			<td>Heat electronic pad</td>
			<td>Cozee Comfort</td>
			<td>n/a</td>
			<td></td>
		</tr>
		<tr>
			<td>6/O silk braided suture</td>
			<td>Harvard Apparatus</td>
			<td>72-3287</td>
			<td></td>
		</tr>
		<tr>
			<td>9/O Dafilon (polyamide) suture</td>
			<td>B-Braun</td>
			<td>G1111434</td>
			<td></td>
		</tr>
		<tr>
			<td>5/O braided silk suture</td>
			<td>Harvard Apparatus</td>
			<td>51-7680</td>
			<td></td>
		</tr>
		<tr>
			<td>Regular bevel needle, 1 inch, 21G</td>
			<td>Becton, Dickinson and Company</td>
			<td>305175</td>
			<td></td>
		</tr>
		<tr>
			<td>1 ml syringe slip tip</td>
			<td>Becton, Dickinson and Company</td>
			<td>300184</td>
			<td></td>
		</tr>
		<tr>
			<td>Wypall paper swabs</td>
			<td>Kimberley-Clark</td>
			<td>L40</td>
			<td>Sterilised (Autoclave)</td>
		</tr>
		<tr>
			<td>Cotton wool buds</td>
			<td>Johnson and Johnson</td>
			<td>n/a</td>
			<td>Sterilised (Autoclave)</td>
		</tr>
		<tr>
			<td>Plain drapes</td>
			<td>Guardian</td>
			<td>CB03</td>
			<td>Sterilised (Autoclave)</td>
		</tr>
		<tr>
			<td>Soft wall silicone rubber tubing</td>
			<td></td>
			<td></td>
			<td>Silicone tubing - internal diameter 1.0 mm; external diameter 2.0 mm; wall thickness 0.6 mm</td>
		</tr>
		<tr>
			<td>(Lacri-Lube) White soft paraffin 57.3%, mineral oil 42.5% and lanolin alcohols 0.2%</td>
			<td>Allergan Ltd</td>
			<td>21956GB10X</td>
			<td></td>
		</tr>
		<tr>
			<td>(Videne) Povidone-iodine 10%</td>
			<td>Ecolab Ltd</td>
			<td>PL 04509/0041</td>
			<td></td>
		</tr>
		<tr>
			<td>(Vetalar V) Ketamine hydrochloride</td>
			<td>Pfizer Animal Health</td>
			<td>Vm 42058/4165</td>
			<td>100mg/ml solution</td>
		</tr>
		<tr>
			<td>(Domitor) Medetomidine hydrochloride</td>
			<td>Orion Pharma</td>
			<td>Vm 06043/4003</td>
			<td>1mg/ml</td>
		</tr>
		<tr>
			<td>(Vetergesic) Bupernorphine hydrochloride</td>
			<td>Alsto Animal Health</td>
			<td>Vm 00063/4002</td>
			<td>0.3mg/ml</td>
		</tr>
		<tr>
			<td>(Antisedan) Atipamezole hydrochoride</td>
			<td>Orion Pharma</td>
			<td>Vm 06043/4004</td>
			<td>5mg/ml</td>
		</tr>
		<tr>
			<td>(Adept) 4% Icodextrin</td>
			<td>Baxter</td>
			<td></td>
			<td>Adhesion reduction solution</td>
		</tr>
		<tr>
			<td>NaCl 0.9%</td>
			<td>Baxter</td>
			<td>FKE1323</td>
			<td></td>
		</tr>
	</tbody>
</table>

a murine model of irreversible and reversible unilateral ureteric obstruction

Obstruction of the kidney may affect native or transplanted kidneys and results in kidney injury and scarring. Presented here is a model of obstructive nephropathy induced by unilateral ureteric obstruction (UUO), which can either be irreversible (UUO) or reversible (R-UUO). In the irreversible UUO model, the ureter may be obstructed for variable periods of time in order to induce increasingly severe renal inflammation and interstitial fibrotic scarring. In the reversible R-UUO model the ureter is obstructed to induce hydronephrosis, tubular dilation and inflammation. After a suitable period of time the ureteric obstruction is then surgically reversed by anastomosis of the severed previously obstructed ureter to the bladder in order to allow complete decompression of the kidney and restoration of urinary flow to the bladder. The irreversible UUO model has been used to investigate various aspects of renal inflammation and scarring including the pathogenesis of disease and the testing of potential anti-inflammatory or anti-fibrotic therapies. The more challenging model of R-UUO has been used by some investigators and does offer significant research potential as it allows the study of inflammatory and immune processes and tissue remodeling in an injured and scarred kidney following the removal of the injurious stimulus. As a result, the R-UUO model offers investigators the opportunity to explore the resolution of kidney inflammation together with key aspects of tissue repair. These experimental models are of relevance to human disease as patients often present with obstruction of the renal tract that requires decompression and are commonly left with significant residual kidney impairment that has no current treatment options and may lead to eventual end stage kidney failure.

Böbrek görünümü değişir belirgin üreter tıkanıklığı takip ve soluk ve zaman palpasyonla gergin (Şekil 1) olur. Tıkanma ve böbrek pelvis üreter proksimalinde artan dilatasyon vardır. böbrek böbrek korteks ve medulla belirgin bir incelme elde uzamış tıkanma ile obstrüktif nefropati artar süresi olarak giderek atrofik hale gelir. Üreter tıkanıklığı iptali sonrasında, böbrek kan akımı artar renk ve doku ödemi giderir da koyulaşır. Onlar uzun süreli şişkinlik dönemin...

Watch this Scientific Journal Video about A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction at JoVE.com

A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction

The murine model of irreversible unilateral ureteric obstruction (UUO) is presented together with the model of reversible UUO in which the ureteric obstruction is relieved by anastomosis of the severed ureter into the bladder. These models enable the study of renal inflammation and scarring as well as tissue remodeling.

Geri dönüşümsüz ve Tersinir Tek taraflı Üreterik Obstrüksiyon bir fare modeli

Obstruction of the kidney may affect native or transplanted kidneys and results in kidney injury and scarring. Presented here is a model of obstructive ...

a-murine-model-irreversible-reversible-unilateral-ureteric

Research

JoVE Journal

Medicine

30.1K Görüntüleme.  University of Edinburgh. The murine model of irreversible unilateral ureteric obstruction (UUO) is presented together with the model of reversible UUO in which the ureteric obstruction is relieved by anastomosis of the severed ureter into the bladder. These models enable the study of renal inflammation and scarring as well as tissue remodeling.

Video: A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction

Creation of Reversible Cholestatic Rat Model

Cholestasis is a clinical condition commonly encountered by both surgeons and gastroenterologists. Cholestasis can cause various physiological changes and affect the nutritional status and surgical outcomes. Study of the pathophysiological changes occurring in the liver and other organs is of importance. Various studies have been done in cholestatic rat models.
We used a reversible cholestatic rat model in our recent study looking at the role of methylprednisolone in the ischemia reperfusion injury. Various techniques for creation of a reversible cholestatic model have been described. Creation of a reversible cholestatic rat model can be challenging in view of the smaller size and unique hepatopancreatobiliary anatomy in rats. This video article demonstrates the creation of a reversible cholestatic model.
This model can be used in various studies, such as looking at the changes in nutritional, physiological, pathological, histological and immunological changes in the gastrointestinal tract. This model can also be used to see the effects of cholestasis and various therapeutic interventions on major hepatic surgeries.

Cholestasis is a clinical condition commonly encountered by both surgeons and gastroenterologists. Creation of a reversible cholestatic rat model can be challenging in view of the smaller size and unique hepatopancreatobiliary anatomy in rats. This video article demonstrates the creation of a reversible cholestatic model.

Tersinir kolestatik Rat Modeli Yaratılış

Cholestasis is a clinical condition commonly encountered by both surgeons and gastroenterologists. Cholestasis can cause various physiological changes and ...

Tıp

A Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor

While the majority of human spinal cord injuries occur in the cervical spinal cord, the vast majority of laboratory research employs animal models of spinal cord injury (SCI) in which the thoracic spinal cord is injured. Additionally, because most human cord injuries occur as the result of blunt, non-penetrating trauma (e.g. motor vehicle accident, sporting injury) where the spinal cord is violently struck by displaced bone or soft tissues, the majority of SCI researchers are of the opinion that the most clinically relevant injury models are those in which the spinal cord is rapidly contused.1 Therefore, an important step in the preclinical evaluation of novel treatments on their way to human translation is an assessment of their efficacy in a model of contusion SCI within the cervical spinal cord. Here, we describe the technical aspects and resultant anatomical and behavioral outcomes of an unilateral contusive model of cervical SCI that employs the Infinite Horizon spinal cord injury impactor.
Sprague Dawley rats underwent a left-sided unilateral laminectomy at C5. To optimize the reproducibility of the biomechanical, functional, and histological outcomes of the injury model, we contused the spinal cords using an impact force of 150 kdyn, an impact trajectory of 22.5&deg; (animals rotated at 22.5&deg;), and an impact location off of midline of 1.4 mm. Functional recovery was assessed using the cylinder rearing test, horizontal ladder test, grooming test and modified Montoya's staircase test for up to 6 weeks, after which the spinal cords were evaluated histologically for white and grey matter sparing.
The injury model presented here imparts consistent and reproducible biomechanical forces to the spinal cord, an important feature of any experimental SCI model. This results in discrete histological damage to the lateral half of the spinal cord which is largely contained to the ipsilateral side of injury. The injury is well tolerated by the animals, but does result in functional deficits of the forelimb that are significant and sustained in the weeks following injury. The cervical unilateral injury model presented here may be a resource to researchers who wish to evaluate potentially promising therapies prior to human translation.

A reliable and repeatable way to produce a cervical unilateral spinal cord injury using the Infinite Horizon impactor is described. The method takes advantage of a custom designed frame and clamp to stabilize the spine. The standardized procedure and biomechanical injury parameters result in sufficient and sustained injuries.

Sonsuz Horizon Darbeli kullanarak tek taraflı Servikal Spinal Kord Yaralanması bir Contusive Modeli

While the majority of human spinal cord injuries occur in the cervical spinal cord, the vast majority of laboratory research employs animal models of ...

A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion

Surgical trauma by thoracotomy in open-chest models of coronary ligation induces an immune response which modifies different mechanisms involved in ischemia and reperfusion. Immune response includes cytokine expression and release or secretion of endogenous ligands of innate immune receptors. Activation of innate immunity can potentially modulate infarct size. We have modified an existing murine closed-chest model using hanging weights which could be useful for studying myocardial pre- and postconditioning and the role of innate immunity in myocardial ischemia and reperfusion. This model allows animals to recover from surgical trauma before onset of myocardial ischemia.
Volatile anesthetics have been intensely studied and their preconditioning effect for the ischemic heart is well known. However, this protective effect precludes its use in open chest models of coronary artery ligation. Thus, another advantage could be the use of the well controllable volatile anesthetics for instrumentation in a chronic closed-chest model, since their preconditioning effect lasts up to 72 hours. Chronic heart diseases with intermittent ischemia and multiple hit models are other possible applications of this model.
For the chronic closed-chest model, intubated and ventilated mice undergo a lateral blunt thoracotomy via the 4th intercostal space. Following identification of the left anterior descending a ligature is passed underneath the vessel and both suture ends are threaded through an occluder. Then, both suture ends are passed through the chest wall, knotted to form a loop and left in the subcutaneous tissue. After chest closure and recovery for 5 days, mice are anesthetized again, chest skin is reopened and hanging weights are hooked up to the loop under ECG control.
At the end of the ischemia/reperfusion protocol, hearts can be stained with TTC for infarct size assessment or undergo perfusion fixation to allow morphometric studies in addition to histology and immunohistochemistry.

Surgical trauma induces an inflammatory response. Cytokines and endogenous ligands are known to modulate myocardial infarct size following ischemia and reperfusion. We present a modified closed-chest model of murine ischemia and reperfusion using hanging weights to minimize effects of thoracotomy.

Miyokard İskemi ve Reperfüzyon bir Mürin Kapalı göğüs Modeli

Surgical trauma by thoracotomy in open-chest models of coronary ligation induces an immune response which modifies different mechanisms involved in ...

Murine Model of Wound Healing

Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. Impaired wound healing, which occurs in diabetic patients for example, can lead to severe unfavorable outcomes such as amputation. There is, therefore, an increasing impetus to develop novel agents that promote wound repair. The testing of these has been limited to large animal models such as swine, which are often impractical. Mice represent the ideal preclinical model, as they are economical and amenable to genetic manipulation, which allows for mechanistic investigation. However, wound healing in a mouse is fundamentally different to that of humans as it primarily occurs via contraction. Our murine model overcomes this by incorporating a splint around the wound. By splinting the wound, the repair process is then dependent on epithelialization, cellular proliferation and angiogenesis, which closely mirror the biological processes of human wound healing. Whilst requiring consistency and care, this murine model does not involve complicated surgical techniques and allows for the robust testing of promising agents that may, for example, promote angiogenesis or inhibit inflammation. Furthermore, each mouse acts as its own control as two wounds are prepared, enabling the application of both the test compound and the vehicle control on the same animal. In conclusion, we demonstrate a practical, easy-to-learn, and robust model of wound healing, which is comparable to that of humans.

A murine model of cutaneous wound healing that can be used to assess therapeutic compounds in physiological and pathophysiological settings.

Yara Şifa murin Modeli

Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. ...

A Murine Model of Subarachnoid Hemorrhage

In this video publication a standardized mouse model of subarachnoid hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of Willis perforation (CWp) and proven by intracranial pressure (ICP) monitoring. Thereby a homogenous blood distribution in subarachnoid spaces surrounding the arterial circulation and cerebellar fissures is achieved. Animal physiology is maintained by intubation, mechanical ventilation, and continuous on-line monitoring of various physiological and cardiovascular parameters: body temperature, systemic blood pressure, heart rate, and hemoglobin saturation. Thereby the cerebral perfusion pressure can be tightly monitored resulting in a less variable volume of extravasated blood. This allows a better standardization of endovascular filament perforation in mice and makes the whole model highly reproducible. Thus it is readily available for pharmacological and pathophysiological studies in wild type and genetically altered mice.

A standardized mouse model of subarachnoid hemorrhage by intraluminal Circle of Willis perforation is described. Vessel perforation and subarachnoid bleeding are monitored by intracranial pressure monitoring. In addition various vital parameters are recorded and controlled to maintain physiologic conditions.

Subaraknoid Kanama bir fare modeli

In this video publication a standardized mouse model of subarachnoid  hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of  Willis ...

A Preclinical Murine Model of Hepatic Metastases

Numerous murine models have been developed to study human cancers and advance the understanding of cancer treatment and development. Here, a preclinical, murine pancreatic tumor model of hepatic metastases via a hemispleen injection of syngeneic murine pancreatic tumor cells is described. This model mimics many of the clinical conditions in patients with metastatic disease to the liver. Mice consistently develop metastases in the liver allowing for investigation of the metastatic process, experimental therapy testing, and tumor immunology research.

A preclinical, murine model of hepatic metastases performed via a hemispleen injection technique.

Karaciğer metastazları Klinik öncesi fare modeli

Numerous murine models have been developed to study human cancers and advance the understanding of cancer treatment and development. Here, a preclinical, ...

Pre-clinical Orthotopic Murine Model of Human Prostate Cancer

To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information about this disease. The human orthotopic prostate cancer xenograft mouse model provides a useful alternative approach for understanding the specific interactions between genetically and molecularly altered tumor cells, their organ microenvironment, and for evaluation of efficacy of therapeutic regimens. This is a well characterized model designed to study the molecular events of primary tumor development and it recapitulates the early events in the metastatic cascade prior to embolism and entry of tumor cells into the circulation. Thus it allows elucidation of molecular mechanisms underlying the initial phase of metastatic disease. In addition, this model can annotate drug targets of clinical relevance and is a valuable tool to study prostate cancer progression. In this manuscript we describe a detailed procedure to establish a human orthotopic prostate cancer xenograft mouse model.

Prostate cancer is the second most common cause of cancer-related deaths in the United States. An orthotopic cancer model provides a useful approach to understand the biology of prostate cancer and to evaluate the efficacy of therapeutic regimens. This protocol describes detailed steps necessary to establish an orthotopic prostate cancer mouse model.

İnsan Prostat Kanseri klinik öncesi Ortotopik murin modeli

To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information ...

Generating a Murine Orthotopic Metastatic Breast Cancer Model and Performing Murine Radical Mastectomy

In vivo mouse models to assess breast cancer progression are essential for cancer research, including preclinical drug developments. However, the majority of the practical and technical details are commonly omitted in published manuscripts which, therefore, makes it challenging to reproduce the models, particularly when it involves surgical techniques. Bioluminescence technology allows for the evaluation of small amounts of cancer cells even when a tumor is not palpable. Utilizing luciferase-expressing cancer cells, we establish a breast cancer orthotopic inoculation technique with a high tumorigenesis rate. Lung metastasis is assessed utilizing an ex vivo technique. We, then, establish a mastectomy model with a low local recurrence rate to assess the metastatic tumor burden. Herein, we describe, in detail, the surgical techniques of orthotopic implantation and mastectomy for breast cancer with a high tumorigenesis rate and low local recurrence rates, respectively, to improve breast cancer model efficiency.

We introduce a murine orthotopic breast cancer model and radical mastectomy model with bioluminescence technology to quantify the tumor burden to mimic human breast cancer progression.

Fare Orthotopic metastatik meme kanseri Model oluşturma ve fare radikal mastektomi gerçekleştirme

In vivo mouse models to assess breast cancer progression are essential for cancer research, including preclinical drug developments. However, the majority ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

İzometrik Contractility ölçüm tel Myography kullanarak fare mezenterik arter

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

A Reversible Silicon Oil-Induced Ocular Hypertension Model in Mice

Elevated intraocular pressure (IOP) is a well-documented risk factor for glaucoma. Here we describe a novel, effective method for consistently inducing stable IOP elevation in mice that mimics the post-operative complication of using silicone oil (SO) as a tamponade agent in human vitreoretinal surgery. In this protocol, SO is injected into the anterior chamber of the mouse eye to block the pupil and prevent inflow of aqueous humor. The posterior chamber accumulates aqueous humor and this in turn increases the IOP of the posterior segment. A single SO injection produces reliable, sufficient, and stable IOP elevation, which induces significant glaucomatous neurodegeneration. This model is a true replicate of secondary glaucoma in the eye clinic. To further mimic the clinical setting, SO can be removed from the anterior chamber to reopen the drainage pathway and allow inflow of aqueous humor, which is drained through the trabecular meshwork (TM) at the angle of the anterior chamber. Because IOP quickly returns to normal, the model can be used to test the effect of lowering IOP on glaucomatous retinal ganglion cells. This method is straightforward, does not require special equipment or repeat procedures, closely simulates clinical situations, and may be applicable to diverse animal species. However, minor modifications may be required.

Here, we present a protocol to induce ocular hypertension and glaucomatous neurodegeneration in mouse eyes by intracameral injection of silicone oil and the procedure for silicone oil removal from the anterior chamber to return elevated intraocular pressure to normal.

Farelerde Geri Dönüşümlü Silikon YağA Bağlı Oküler Hipertansiyon Modeli

Elevated intraocular pressure (IOP) is a well-documented risk factor for glaucoma. Here we describe a novel, effective method for consistently inducing ...