The work was funded by a CHIR operating grant (DJB).

下面的实验方案经该机构的动物护理委员会。 1. NEMO雌性大鼠<ol><li> 制备 <ol><li>放置一个雌性Sprague-Dawley大鼠重约200克在3％异氟烷麻醉，称重动物，和剃以及使用碘手术擦洗消毒前耻骨区的3倍。 </li><li>在加热垫上，磁带后肢和尾部向下和导尿与20号血管导管，其也被轻轻贴，以防止滑动膀胱。 </li></ol></li><li> 解剖 <ol><li>使用手术刀从朝向尿道口的可触知的耻骨联合执行8mm的纵向皮肤切口。抬离皮肤两边便于以后伤口闭合。 </li><li>解剖直截了当地通过用细剪刀纵向扩展来识别带支架尿道。将细自保持皮肤挂钩，以提高曝光尿道。 </li><li>执行一些温和纵向使用弯剪背侧到尿道开发尿道和阴道之间的平面扩展。然后，通过直言尿道后面的4-0丝线缝合，并准备一个外科医生的结双拐。 </li></ol></li><li> 部分尿道梗阻 <ol><li>除去血管导管，放置平行于尿道0.9毫米金属棒，然后拧紧围绕尿道和金属杆的结，从而使后者仍然其后容易滑出。 </li><li>固定结用3更抛出使用温和张力移除所述杆之前。切缝合线端部约3姆·隆恩，或者4毫米如果梗阻后释放实验的一部分。 </li></ol></li><li> 伤口闭合 <ol><li>近似使用可吸收缝线编织4-0埋单针在尿道旁腺。 </li><li>用埋水平褥式缝合使用相同的吸收SUT关闭皮肤URE。注意:尽管它可能看起来非常规使用的可吸收缝合线的皮肤穿透针，我们没有遇到的并发症，如伤口感染，并且能够避免拆线。 </li></ol></li><li> 术后护理 <ol><li>注入丁丙诺啡0.1mg / kg的皮下放置在大鼠恢复笼之前。 </li><li>提供一些软恢复饮食的头24个小时的单坐落老鼠。在此之后，再次房子的动物在同一对作为前道工序提供他们正在做的很好，属于同一个治疗组。 </li><li>每天检查大鼠膀胱大小和总体幸福感;记录自己的体重至少每周一次。 </li></ol></li></ol> 2. NEMO雌性小鼠<ol><li> 制备 <ol><li>放置一个雌性C57BL / 6小鼠体重约为18 g，并且继续进行在步骤1.1.1为详细。 </li><li>继续进行在步骤1.1.2详细的，除了使用24量规昂iocatheter。 </li></ol></li><li> 解剖 <ol><li>使用手术刀进行6 mm纵向皮肤切口，从可触诊的耻骨联合朝向尿道口。 </li><li>直截了当地用精细剪刀纵向扩张来识别支架置入的尿道。通过类似的钝性剥离来解除在尿道上腹部运行的神经 - 血管束。 </li><li>使用弯曲的剪刀对尿道进行一些柔和的纵向展开，以在尿道和阴道之间形成平面。然后，直截了当地穿过尿道后面的5-0不可吸收的编织缝线，并准备外科医生结的双掷。 </li></ol></li><li> 部分尿道梗阻 <ol><li>将血管导管与1 mL注射器连接，并将0.1 mL生理盐水注入膀胱。 </li><li>将26号套管平行于尿道放置。轻轻收紧尿道和套管周围的结，同时拉回血管日。 </li><li>固定结用3更抛出使用温和张力移除插管之前。 </li><li>测试尿液出现在在对动物的膀胱温和的压力，尿道口;如果无法表达尿松开领带。否则，切缝合线端部约3姆·隆恩。 </li></ol></li><li> 伤口闭合 <ol><li>使用5-0编织可吸收缝合线埋藏水平褥式缝合关闭皮肤。 </li></ol></li><li> 术后护理 <ol><li>将小鼠放入在回收笼子之前注入0.1mg / kg的丁丙诺啡皮下注射。 </li><li>提供一些软恢复饮食的头48个小时，以单一坐落鼠标。在此之后，再次房子动物同组的过程之前，只要它们做得很好，属于同一个治疗组。 注:小鼠在手术后可触及的膀胱胀得24小时处理被过度阻塞时不作废，并会在n内死亡EXT 1 - 2天，除非麻醉下带回了去除阻碍结扎。 </li><li>每天检查小鼠膀胱大小和总体幸福感;记录自己的体重至少每周一次。 </li></ol></li></ol>

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J., 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=Early+Sequential+Changes+in+Bladder+Function+after+Partial+Bladder+Outlet+Obstruction+in+Awake+Sprague-Dawley+Rats:+Focus+on+the+Decompensated+Bladder.">Early Sequential Changes in Bladder Function after Partial Bladder Outlet Obstruction in Awake Sprague-Dawley Rats: Focus on the Decompensated Bladder.</a> Korean J Urol. 52 (12), 835-837 (2011).</li><li>Schroeder, A., 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=Protective+effect+of+an+oral+endothelin+converting+enzyme+inhibitor+on+rat+detrusor+function+after+outlet+obstruction.">Protective effect of an oral endothelin converting enzyme inhibitor on rat detrusor function after outlet obstruction.</a> J Urol. 172 (3), 1171-1174 (2004).</li><li>Sidler, M., Aitken, K., Jiang, J., Bijos, D., B&#228;gli, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term="sometimes+a+sham+is+just+a+sham"+-+why+the+rodent+model+of+partial+bladder+outlet+obstruction+needs+adjustment.">"sometimes a sham is just a sham" - why the rodent model of partial bladder outlet obstruction needs adjustment.</a> J Urol. 195 (4), e379 (2016).</li><li>Jin, L. 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The authors have nothing to disclose.

动物死亡率在许多报告10，11，13 pBOO的传统模式在近端尿道的主要问题，在15％以上的。 NEMO出现时在雌性大鼠施加到具有最小的死亡率。在小鼠近端尿道梗阻在技术上更具挑战性比在大鼠，因而更容易出现并发症。使用26号套管作为我们中间尿道方式的占位符，我们只有最小的动物死亡。在这里我们使用26号插管18...

部分膀胱出口梗阻（pBOO）具有高患病率，并可能导致严重的膀胱功能障碍1;频谱范围从先天畸形如后尿道瓣膜或尿道下裂，在获取的尿道狭窄良性前列腺增生。影响男性六十多年超过30％及以上2后者。大患者的负担，并与相关pBOO巨大的医疗费用担保的大量研究工作投入研究膀胱重塑响应增加流出阻力3。从2006年到2015年，超过220考研收录的论文进行了关于pBOO对膀胱的作用发表。 虽然pBOO动物模型已被设计在若干物种4，大鼠5，兔子6，猪7和谅解备忘录如E 8， 图9，但可以说是最常用的动物模型是经历近端尿道的局部阻塞的雌性大鼠;进入动物的腹部，膀胱外缝合，和解剖膀胱颈周围是不可避免的与这种传统的近端尿道梗阻技术。变异梗阻和动物死亡的程度仅仅是一些与此过程10，11相关联的关注;我们发现，在假手术的动物，围绕近端尿道切开导致，在膀胱颈12的神经纤维损失相关的生理变化。这一调查结果表明，这是最常用的pBOO动物模型，这涉及访问雌性啮齿动物的近端尿道，导致去神经损伤膀胱的相关结构和功能的改变，从而影响假和阻碍动物。因此，需要另一种方法避免去神经损伤。我们的实验室开发并评估了保留神经的中期尿道梗阻（NEMO）的方式，有效地促使膀胱预期梗阻相关的变化，如器官的质量和残余尿增多，而假手术的动物是来自非手术对照组动物没有区别。此外，横纹尿道括约肌仍保持不变，因为它位于靠近夹层的水平。此外，变异在膀胱质量梗阻引起的增加比在传统的近端尿道梗阻显著下和动物死亡率为零。 我们还成功地应用尼莫在雌性小鼠在阻碍动物低于10％的死亡率，而迄今为止描述的所有小鼠模型pBOO用约50％的死亡率相关。在研究小鼠膀胱重塑pBOO的上下文将与applicabil受益转基因修饰的全谱，两者均。 围绕在女性啮齿动物中尿道解剖不诱导在传统的近端梗阻模型中观察到的膀胱不希望的和混杂结构或功能的改变。然而，在中间尿道水平诱导部分阻塞仍引起膀胱肥大和增加的残余尿，从动物模型pBOO预期。重要的是，在小鼠进行尼莫在打开膀胱pBOO以重塑转基因方法，这在较大的啮齿动物几乎无法进行调查。

<table><tbody><tr><td>Female rat&amp;nbsp;</td><td>Charles-River Canada</td><td>Sprague Dawley Rat (Crl:SD); Strain Code: 400</td><td>about 200 g</td></tr><tr><td>Isoflorane vaporizer</td><td>Benson medical industries inc.</td><td>TEC III Isoflurane; product code: 53-T3ISO&amp;nbsp;</td><td></td></tr><tr><td>Isoflorane</td><td>Fresenius Kabi Animal Health</td><td>Isoflorane; product code CP0406V2</td><td>&amp;nbsp;250 mL bottle</td></tr><tr><td>Disposable scalpel</td><td>Ted Pella, Inc.</td><td>#15 Sterile, Stainless Steel Scalpels; catalogue number 549-9-15S</td><td></td></tr><tr><td>Microscopy forceps</td><td>Ted Pella, Inc.</td><td>Aesculap Microscopy Forceps, Finepoint, 115mm; product number 5443</td><td></td></tr><tr><td>Adson forceps</td><td>Ted Pella, Inc.</td><td>Aesculap Adson Dissection Forceps, Curved, 120mm; product number 5002-9</td><td></td></tr><tr><td>Curved surgical scissors</td><td>Ted Pella, Inc.</td><td>Surgical Scissors, Curved, S/S, 105mm; catalogue number 1376</td><td></td></tr><tr><td>0.9 mm inox metal rod</td><td>goodfellow.com</td><td>Stainless Steel - AISI 316L Wire Diameter:0.9mm; order code 911-684-65</td><td></td></tr><tr><td>Skin hooks - self made from inox steel</td><td>goodfellow.com</td><td>Stainless Steel - AISI 316L Wire Diameter:0.9mm; order code 911-684-65</td><td></td></tr><tr><td>4-0 Silk suture</td><td>esutures.com</td><td>4-0 Sofsilk black 98&quot; strand; product number LS640</td><td></td></tr><tr><td>5-0 Vicry suture</td><td>esutures.com</td><td>5-0 Vicryl undyed 27&quot; RB-1 taper; product number J213H</td><td></td></tr><tr><td>Needle holder</td><td>Medsupplier.com</td><td>Integra Miltex Carb-N-Sert Baumgartner Needle Holder - 5 1/2&quot;; product code SKU NEE4484-8-40TC&lt;br/&gt; SKU NEE4484-8-40TC&lt;br/&gt; SKU NEE4484-8-40TC&amp;nbsp;</td><td></td></tr><tr><td>Temgesic (Buprenorphine)</td><td>first veterinary supply</td><td>Buprenex 0.3MG/ml inj amps; item #075701</td><td></td></tr><tr><td>1 mL syringe with 27 G needle</td><td>Fisher Scientific</td><td>BD&amp;nbsp;Tuberculin Syringe, BD 309623</td><td></td></tr><tr><td>20 G Angiocath</td><td>Fisher Scientific</td><td>Andwin Scientific&amp;nbsp;ANGIOCATH 20 GA; Catalog No. NC9561906</td><td></td></tr><tr><td>Recovery diet</td><td>clearh2o</td><td>DietGel 31M; 72-08-5022</td><td></td></tr><tr><td>C57Bl/6 female mice</td><td>Charles-River Canada</td><td>C57BL/6 Mouse (C57BL/6NCrI); Strain Code: 027</td><td>about 18 g</td></tr><tr><td>24 G angiocath</td><td>Fisher Scientific</td><td>Hanna Pharmaceutical Supply Co., Inc.&amp;nbsp;IV CATH ANGIOCATH 24GX3/4IN; Catalog No. NC9814340</td><td></td></tr><tr><td>5-0 Ethibond</td><td>esutures.com</td><td>5-0 Ethibond green 30&quot; RB-1 taper; product number X550H</td><td></td></tr><tr><td>26 G syringe needle</td><td>Sigma-Aldrich</td><td>BD Precisionglide syringe needle, Gauge 26; z192392</td><td></td></tr><tr><td>Normal Saline</td><td>Baxter</td><td>0.9% Sodium Chloride Injection, USP, 100 mL MINI-BAG; product code 2B0043</td><td></td></tr></tbody></table>

nerve-sparing mid-urethral obstruction (nemo) in female small rodents

部分膀胱出口阻塞（pBOO）患病率高，导致患者重大负担，医疗费用巨大。在pBOO中调查膀胱重塑的最常见的动物模型是在近端尿道部分阻塞的雌性啮齿动物。梗阻程度和动物死亡率的变异性是近端梗阻的主要问题。此外，围绕近端尿道和膀胱颈的解剖危及膀胱神经支配。 我们为pBOO开发了一种神经节省的中尿道梗阻（NeMO）模型，避免了传统模型的缺点。我们靠近耻骨联合的尿道，这消除了在这个区域的剖腹术和解剖的需要;另外，条纹尿道括约肌仍然保持不变。我们在女性Sprague-Dawley大鼠（12个障碍物，6只假动物）以及雌性C57 / bl6小鼠（20个阻塞物）中进行了NeMOS，18只深水动物）。两周后，我们评价膀胱功能，膀胱质量和体重。 我们有obstructed-或假手术雌性大鼠中没有死亡;作为传统的近端pBOO-方法所描述的，我们绑缝合线围绕近端尿道和暂时放置0.9毫米金属棒。 NEMO诱导膀胱质量增加85％后两周，平均残尿量为0.4mL中部分阻塞的大鼠，而只有0.03 mL，在假手术的动物。在小鼠中，我们测试了3种尺寸捆扎缝线当我们沿尿道放置插管。我们发现，使用27号插管导致超过50％的动物的死亡率;放置25号插管没有产生在膀胱质量增加所需的响应;利用26号插管产生具有最小的动物的死亡率（1/8），但在膀胱质量显著增加2倍良好的结果。

在雌性大鼠神经保留中期尿道梗阻（NEMO） 死亡 我们超过40雌性大鼠进行了中期尿道梗阻，到目前为止，并没有死亡。 膀胱质量 平均相对膀胱质量（膀胱到身体质?...

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Nerve-sparing Mid-urethral Obstruction NeMO in Female Small Rodents

在啮齿类动物中局部膀胱出口梗阻的传统的建模是充满动物死亡率。来自各地的近端尿道和膀胱颈淋巴结清扫术一去神经损伤是主要关注的也是。我们制定并评估了安全可靠的中期，尿道梗阻模型，避免了传统模式的不足。

在女小鼠害保留神经的中期尿道梗阻（NEMO）

Partial bladder outlet obstruction (pBOO) has a high prevalence, causes significant patient burden, and immense health care costs. The most common animal ...

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Nerve-sparing Mid-urethral Obstruction (NeMO) in Female Small Rodents

9.6K 次观看.  The Hospital for Sick Children. 在啮齿类动物中局部膀胱出口梗阻的传统的建模是充满动物死亡率。来自各地的近端尿道和膀胱颈淋巴结清扫术一去神经损伤是主要关注的也是。我们制定并评估了安全可靠的中期，尿道梗阻模型，避免了传统模式的不足。 

视频: Nerve-sparing Mid-urethral Obstruction NeMO in Female Small Rodents

Transurethral Induction of Mouse Urinary Tract Infection

Uropathogenic bacterial strains of interest are grown on agar. Generally, uropathogenic E. coli (UPEC) and other strains can be grown overnight on Luria-Bertani (LB) agar at 37&deg;C in ambient air. UPEC strains grow as yellowish-white translucent colonies on LB agar. Following confirmation of appropriate colony morphology, single colonies are then picked to be cultured in broth. LB broth can be used for most uropathogenic bacterial strains. Two serial, overnight LB broth cultures can be employed to enhance expression of type I pili, a well-defined virulence factor for uropathogenic bacteria. Broth cultures are diluted to the desired concentration in phosphate buffered saline (PBS). Eight to 12 week old female mice are placed under isoflurane anesthesia and transurethrally inoculated with bacteria using polyethylene tubing-covered 30 gauge syringes. Typical inocula, which must be empirically determined for each bacterial/mouse strain combination, are 106 to 108 cfu per mouse in 10 to 50 microliters of PBS. After the desired infection period (one day to several weeks), urine samples and the bladder and both kidneys are harvested. Each organ is minced, placed in PBS, and homogenized in a Blue Bullet homogenizer. Urine and tissue homogenates are serially diluted in PBS and cultured on appropriate agar. The following day, colony forming units are counted.

This video will demonstrate methods to transurethrally induce mouse urinary tract infections and quantify the extent of resulting infections.

经尿道诱导小鼠尿路感染

Uropathogenic bacterial strains of interest are grown on agar. Generally, uropathogenic E. coli (UPEC) and other strains can be grown overnight on ...

科研

免疫与感染

The Use of Cystometry in Small Rodents: A Study of Bladder Chemosensation

The lower urinary tract (LUT) functions as a dynamic reservoir that is able to store urine and to efficiently expel it at a convenient time. While storing urine, however, the bladder is exposed for prolonged periods to waste products. By acting as a tight barrier, the epithelial lining of the LUT, the urothelium, avoids re-absorption of harmful substances. Moreover, noxious chemicals stimulate the bladder's nociceptive innervation and initiate voiding contractions that expel the bladder's contents. Interestingly, the bladder's sensitivity to noxious chemicals has been used successfully in clinical practice, by intravesically infusing the TRPV1 agonist capsaicin to treat neurogenic bladder overactivity1. This underscores the advantage of viewing the bladder as a chemosensory organ and prompts for further clinical research. However, ethical issues severely limit the possibilities to perform, in human subjects, the invasive measurements that are necessary to unravel the molecular bases of LUT clinical pharmacology. A way to overcome this limitation is the use of several animal models2. Here we describe the implementation of cystometry in mice and rats, a technique that allows measuring the intravesical pressure in conditions of controlled bladder perfusion.
	After laparotomy, a catheter is implanted in the bladder dome and tunneled subcutaneously to the interscapular region. Then the bladder can be filled at a controlled rate, while the urethra is left free for micturition. During the repetitive cycles of filling and voiding, intravesical pressure can be measured via the implanted catheter. As such, the pressure changes can be quantified and analyzed. Moreover, simultaneous measurement of the voided volume allows distinguishing voiding contractions from non-voiding contractions3.
	Importantly, due to the differences in micturition control between rodents and humans, cystometric measurements in these animals have only limited translational value4. Nevertheless, they are quite instrumental in the study of bladder pathophysiology and pharmacology in experimental pre-clinical settings. Recent research using this technique has revealed the key role of novel molecular players in the mechano- and chemo-sensory properties of the bladder.

Cystometry is an efficient technique to measure bladder function of small animals in vivo. The bladder is continuously infused at rates controlled through an intravesical catheter, whereas the urethra is left free for micturition. This allows for repetitive filling and emptying of the bladder, while intravesical pressure and voided volume are recorded.

的的膀胱测压小老鼠：A膀胱Chemosensation研究的使用

	The lower urinary tract (LUT) functions as a  dynamic reservoir that is able to store urine and to efficiently expel it at a  convenient time. While ...

医学

Urinary Tract Infection in a Small Animal Model: Transurethral Catheterization of Male and Female Mice

Urinary tract infections (UTI) are extremely common worldwide, incurring significant morbidity and healthcare-associated expenses. Small animal models, which accurately reflect disease establishment and progression, permit dissection of host-pathogen interactions and generation of immunity to infection. In mice, intravesical instillation of uropathogenic E. coli, the causative agent in more than 85% of community acquired UTI, recapitulates many of the stages of infection observed in humans. Until recently, however, UTI could only be modeled in female animals. This limitation has hindered the study of sex-related differences in UTI, as well as other bladder pathologies, such as cancer. Here, we describe a method to instill male mice that allows direct comparison between female and male animals and provide a detailed protocol to assess bladder tissue by flow cytometry as a means to better understand host responses to infection. Together, these approaches will aid in the identification of host factors that contribute to sex biases observed in UTI and other bladder-associated diseases.

The established model of transurethral catheterization of mice allows the study of bladder pathologies, including urinary tract infection, but can only be performed in females. A new model of male transurethral instillation, presented here, will enable research in an area marked by strong clinical and epidemiological differences between the sexes.

小动物模型尿路感染的实验研究: 男性和女性的经尿道插管

Urinary tract infections (UTI) are extremely common worldwide, incurring significant morbidity and healthcare-associated expenses. Small animal models, ...

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.

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.

的不可逆和可逆单侧输尿管梗阻小鼠模型

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

In Vivo Luminal Measurement of Distension-Evoked Urothelial ATP Release in Rodents

ATP, released from the urothelium in response to bladder distension, is thought to play a significant sensory role in the control of micturition. Therefore, accurate measurement of urothelial ATP release in a physiological setting is an important first step in studying the mechanisms that control purinergic signaling in the urinary bladder. Existing techniques to study mechanically evoked urothelial ATP release utilize cultured cells plated on flexible supports or bladder tissue pinned into Ussing chambers; however, each of these techniques does not fully emulate conditions in the intact bladder. Therefore, an experimental setup was developed to directly measure ATP concentrations in the lumen of the rodent urinary bladder.
In this setup, the bladders of anesthetized rodents are perfused through catheters in both the dome of the bladder and via the external urethral orifice. Pressure in the bladder is increased by capping the urethral catheter while perfusing sterile fluid into the bladder through the dome. Measurement of intravesical pressure is achieved using a pressure transducer attached to the bladder dome catheter, akin to the setup used for cystometry. Once the desired pressure is reached, the urethral catheter's cap is removed, and fluid collected for ATP quantification by luciferin-luciferase assay. Through this experimental setup, the mechanisms controlling both mechanical and chemical stimulation of urothelial ATP release can be interrogated by including various agonists or antagonists into the perfusate or by comparing results between wildtype and genetically modified animals.

In Vivo Luminal Measurement of Distension-Evoked Urothelial ATP Release in Rodents

This protocol describes the procedure for measuring ATP concentrations in the lumen of the bladder in an anesthetized rodent.

体内 啮齿动物膨胀诱发尿路上皮ATP释放的管腔测量

ATP, released from the urothelium in response to bladder distension, is thought to play a significant sensory role in the control of micturition. ...

Development of a Uterosacral Ligament Suspension Rat Model

Pelvic organ prolapse (POP) is a common pelvic floor disorder (PFD) with the potential to significantly impact a woman's quality of life. Approximately 10%-20% of women undergo pelvic floor repair surgery to treat prolapse in the United States. PFD cases result in an overall $26.3 billion annual cost in the United States alone. This multifactorial condition has a negative impact on the quality of life and yet the treatment options have only dwindled in the recent past. One common surgical option is uterosacral ligament suspension (USLS), which is typically performed by affixing the vaginal vault to the uterosacral ligament in the pelvis. This repair has a lower incidence of complications compared to those with mesh augmentation, but is notable for a relatively high failure rate of up to 40%. Considering the lack of standard animal models to study pelvic floor dysfunction, there is an urgent clinical need for innovation in this field with a focus on developing cost-effective and accessible animal models. In this manuscript, we describe a rat model of USLS involving a complete hysterectomy followed by fixation of the remaining vaginal vault to the uterosacral ligament. The goal of this model is to mimic the procedure performed on women to be able to use the model to then investigate reparative strategies that improve the mechanical integrity of the ligament attachment. Importantly, we also describe the development of an in situ tensile testing procedure to characterize interface integrity at chosen time points following surgical intervention. Overall, this model will be a useful tool for future studies that investigate treatment options for POP repair via USLS.

Pelvic organ prolapse affects millions of women worldwide and yet some common surgical interventions have failure rates as high as 40%. The lack of standard animal models to investigate this condition impedes progress. We propose the following protocol as a model for uterosacral ligament suspension and in vivo tensile testing.

子宫骶韧带悬浮大鼠模型的开发

Pelvic organ prolapse (POP) is a common pelvic floor disorder (PFD) with the potential to significantly impact a woman's quality of life. Approximately ...

Urethral Stricture Induction Followed by Buccal Mucosa Graft Urethroplasty in a Rat Model

Urethral reconstruction is an important area of expertise for urologists. The buccal mucosa is considered the best option when urethral grafting is necessary, although in some cases, it is inappropriate or needs to be optimized to repair a given stricture. Therefore, developing innovative procedures and evaluating their putative success in experimental models is crucial to fit the clinical need. With this goal, this study describes a protocol in which urethral stricture was induced by electrocautery in Wistar rats. Urethral reconstruction was performed 1 week later with a buccal mucosa graft, harvested from the lower lip, and placed in a ventral onlay fashion. A retrograde urethrogram showed a significant improvement in urethral diameter after urethroplasty compared to the respective value after stricture induction. Additionally, the graft placement was assessed by blood perfusion analysis using laser Doppler. As expected, a dark blue area corresponded to the non-vascularized buccal mucosa graft. This procedure can successfully simulate the normal pathophysiological process of urethral injury and tissue modulation, as well as urethral reconstruction using a buccal mucosa graft in a reproducible manner, and serve as the basis for future research based on tissue engineering or urethral grafts.

In the present protocol, a urethral stricture induction was developed in Wistar rats, followed by urethral reconstruction with a buccal mucosa graft. A retrograde urethrogram and laser Doppler assessment were performed, validating urethral reconstruction (after stricture formation) and graft placement.

大鼠模型中的尿道狭窄诱导后进行颊粘膜移植尿道成形术

Urethral reconstruction is an important area of expertise for urologists. The buccal mucosa is considered the best option when urethral grafting is ...

<meta charset="utf8"></head><body>尿道狭窄的高效大鼠模型：电刀法

Iatrogenic Injury Recapitulated: Electroexcision Technique for Urethral Stricture Modeling in Rats

Urethral stricture (US) is a common clinical condition in urology, characterized by high prevalence and morbidity across all ages. Current treatments for US, such as urethral dilatation and internal urethrotomy, fail to fully resolve the condition and are associated with high rates of recurrence and complications. 
Additionally, the pathogenesis of US is not well understood. To explore the pathogenesis of US and develop new therapeutic strategies, it is crucial to establish a standardized rat model that accurately reflects the clinical manifestations. This study outlines a straightforward and repeatable method for inducing US in rats using a high-frequency electric knife. The method involves making a longitudinal incision with the electric knife set to a unipolar mixed cutting mode at 4 W, which inflicts significant urethral damage. Histopathological analysis shows thickening of the urothelium, inflammatory infiltration, and disorganized collagen fibers. This model effectively replicates iatrogenic injury through electroexcision in the rat urethra. In summary, this study successfully establishes a new, efficient, and stable rat model of US that closely mimics the clinical scenario, providing a valuable tool for further research into the mechanisms and novel treatments for US.

<meta charset="utf8"></head><body>医源性损伤概括：电切除技术在大鼠尿道狭窄建模中的应用

In this study, we present a novel, efficient, and stable rat model of urethral stricture created through electroexcision of the rat urethra, which effectively simulates iatrogenic injury observed in clinical settings.

医源性损伤概括：电切除技术在大鼠尿道狭窄建模中的应用

Urethral stricture (US) is a common clinical condition in urology, characterized by high prevalence and morbidity across all ages. Current treatments for ...

在女小鼠害保留神经的中期尿道梗阻（NEMO）

摘要

探索更多视频

经尿道诱导小鼠尿路感染

的的膀胱测压小老鼠：A膀胱Chemosensation研究的使用

小动物模型尿路感染的实验研究: 男性和女性的经尿道插管

的不可逆和可逆单侧输尿管梗阻小鼠模型

体内啮齿动物膨胀诱发尿路上皮ATP释放的管腔测量

子宫骶韧带悬浮大鼠模型的开发

大鼠模型中的尿道狭窄诱导后进行颊粘膜移植尿道成形术

医源性损伤概括：电切除技术在大鼠尿道狭窄建模中的应用

医源性损伤概括：电切除技术在大鼠尿道狭窄建模中的应用

医源性损伤概括：电切除技术在大鼠尿道狭窄建模中的应用

在女小鼠害保留神经的中期尿道梗阻（NEMO）

摘要

探索更多视频

经尿道诱导小鼠尿路感染

的的膀胱测压小老鼠：A膀胱Chemosensation研究的使用

小动物模型尿路感染的实验研究: 男性和女性的经尿道插管

的不可逆和可逆单侧输尿管梗阻小鼠模型

体内 啮齿动物膨胀诱发尿路上皮ATP释放的管腔测量

子宫骶韧带悬浮大鼠模型的开发

大鼠模型中的尿道狭窄诱导后进行颊粘膜移植尿道成形术

医源性损伤概括：电切除技术在大鼠尿道狭窄建模中的应用

医源性损伤概括：电切除技术在大鼠尿道狭窄建模中的应用

医源性损伤概括：电切除技术在大鼠尿道狭窄建模中的应用

体内啮齿动物膨胀诱发尿路上皮ATP释放的管腔测量