Name: a mouse 5/6th nephrectomy model that induces experimental uremic cardiomyopathy
Uploaded: 2017-11-07T12:30:00
Description: Watch this Scientific Journal Video about A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy at JoVE.com

Dette arbeidet ble støttet av NIH R15 1R15DK106666-01A1 (til J. Liu) og NIH RO1 HL071556 (å Ji Shapiro).

alle dyr omsorg og eksperimenter ble godkjent av Marshall University institusjonelle dyr omsorg og bruk Committee (IACUC) i henhold til National Institutes of Health (NIH) Guide og bruk av forsøksdyr. Mannlige C57BL/6 mus (10-12 uker gamle) ble plassert i en patogen gratis dyr anlegg i utpekte rom med bur som leverer renset luften under en 12t lys/mørke syklus. Mat og vann ble levert ad libitum.
 1. kirurgi forberedelse Merk: den kirurgiske instrumenter o...

<ol>
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M., Himmelfarb, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tipping+the+redox+balance+of+oxidative+stress+in+fibrogenic+pathways+in+chronic+kidney+disease.">Tipping the redox balance of oxidative stress in fibrogenic pathways in chronic kidney disease.</a> Pediatr Nephrol. 24 (12), 2309-2319 (2009).</li><li>Himmelfarb, J., Stenvinkel, P., Ikizler, T. A., Hakim, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+elephant+in+uremia:+oxidant+stress+as+a+unifying+concept+of+cardiovascular+disease+in+uremia.">The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia.</a> Kidney Int. 62 (5), 1524-1538 (2002).</li><li>Becker, B. N., Himmelfarb, J., Henrich, W. L., Hakim, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reassessing+the+cardiac+risk+profile+in+chronic+hemodialysis+patients:+a+hypothesis+on+the+role+of+oxidant+stress+and+other+non-traditional+cardiac+risk+factors.">Reassessing the cardiac risk profile in chronic hemodialysis patients: a hypothesis on the role of oxidant stress and other non-traditional cardiac risk factors.</a> J Am Soc Nephrol. 8 (3), 475-486 (1997).</li><li>Drummond, C. 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Rotta 5/6th PNx modellen har vært mye brukt til å studere Parallelt. På grunn av den mye mindre nyre størrelsen i mus er klassisk arterien ligatur og pole reseksjon svært utfordrende i musen modeller med mulig høy dødelighet og uventet blødning/blod tap.
Vi vedtatt en mus PNx modell med pole hemorroider å overvinne blødning/blod tap. Denne PNx modellen tar mindre tid med bedre overlevelse og høy reproduserbarhet. Denne pole ligation modellen utvikler fenotypiske endringer...

Parallelt, også kjent som kronisk nyresvikt, er en progressiv tap av nyrefunksjon over tid etter hvert utvikler seg til permanent nyresvikt. Parallelt, fra tidlig stadium nyresykdom stater til end-stage renal disease (ESRD), er en stor risikofaktor for hjerte-og karsykdommer hendelser og dødelighet, og gradvis utvikler til kliniske fenotypen kalt "uremisk kardiomyopati"1, 2,3. Den uremisk kardiomyopati hos pasienter med Parallelt eller ESRD er assosiert med kardiovaskulær unormalt, hovedsakelig forårsaket av overbelastning av venstre ventrikkel (LV) Trykk og/eller volum, fører til LV hypertrophy (LVH), LV dilatasjon og LV systolisk dysfunksjon4 ,5,6. CARDIAC fibrose er en annen vanlig patologiske prosessen med uremisk kardiomyopati som reduserer hjerte samsvar resulterer i LV diastolisk dysfunksjon. Alvorlige kardiale fibrose kan føre til plutselig hjertestans død selv i de uten kardiale symptomer7.
5/6th PNx er en brukte CKD dyr modell for dyrestudier med nyresvikt, uremisk kardiomyopati og hypertensjon. PNx oppnås ved ablasjon av 5/6 nyre parenchyma. Rotte modell ble opprinnelig utviklet med de to mest vanlige protokoller ansatt kirurgisk resection eller hjerteinfarkt. Rat PNx modellen er en svært nyttig modell å studere uremisk kardiomyopati med betydelige høyder i blodtrykk, hjerte-hypertrofi og svekket diastolisk funksjon. Senere ble musen PNx modeller, drives med lignende teknikker som rotte modell, utviklet på grunn av bred tilgjengelighet og brukervennlighet gjør genetisk manipulasjon i musen systemet.
Det er godt dokumentert at systemisk oksiderende stress er en konstant funksjon i både kliniske og eksperimentelle uremisk kardiomyopati8,9. Videre oksiderende stress bidrar til uremisk syndrom10og spiller en avgjørende rolle i patogenesen av kardial unormalt i uremisk kardiomyopati11,12,13. Til dette punktet, har vi vist at gnagere 5/6th PNx modell forårsaker fysiologiske morfologiske og biokjemiske funksjoner uremisk kardiomyopati14,15,16, 17. i musen PNx modellen beskrevet her, PNx-opererte musene utviklet betydelige oksidativt stress, minst delvis mediert av Na/K-ATPase signalnettverk funksjon, som er avgjørende for PNx-mediert eksperimentell uremisk kardiomyopati. Demping av Na/K-ATPase signalene ikke bare reduserer oksidativt forsterkning, men også ameliorates phenotypical endringene i PNx-mediert eksperimentell uremisk kardiomyopati18.

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			<td>Hilltop Lab Animals Inc.</td>
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			<td>FUJIFILM VisualSonics Inc.</td>
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			<td>Crystal Chem. Inc.</td>
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			<td>MyBioSource Inc&#160;</td>
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a mouse 5/6th nephrectomy model that induces experimental uremic cardiomyopathy

Kronisk nyresykdom (Parallelt) er en stor risikofaktor for hjerte-og karsykdommer hendelser og dødelighet, og utvikler gradvis til kliniske fenotypen kalt "uremisk kardiomyopati". Her beskriver vi en eksperimentell CKD musemodell, kalt 5/6th delvis nephrectomy (PNx) med pole ligation, som utviklet uremisk kardiomyopati på fire uker etter operasjonen. Denne PNx-modellen ble utført av en to-trinns kirurgi. I trinn-ett kirurgi, var begge poler av venstre nyre samskrevet. Trinn to kirurgi, som ble utført 7 dager etter trinn-ett operasjonen, ble høyre nyre fjernet. De samme kirurgi prosedyrene ble utført humbug kirurgi, men uten pole ligation av venstre nyre eller fjerning av høyre nyrene. De kirurgiske prosedyrene er enklere og mindre tidkrevende, sammenlignet med andre metoder. Imidlertid levningen funksjonelle nyre masse kontrolleres ikke like lett som den nyre arterien hemorroider. Fire uker etter operasjonen med humbug-opererte musene, PNx musene utviklet svekket nyre-funksjon, anemi, hjerte-hypertrofi, hjerte fibrose og redusert hjertefunksjon systolisk og diastolisk.

Dataene viser at dette endret 5/6th PNx modell av pole hemorroider er en enkel og effektiv modell å undersøke uremisk kardiomyopati. På fire uker etter operasjonen, denne PNx modellen presenterer svekket nyre-funksjon, anemi, hjerte-hypertrofi, hjerte fibrose og redusert systolisk og diastolisk hjertefunksjon. Resultatene er oppsummert nedenfor.
På fire uker etter operasjonen utviklet PNx musene s...

Watch this Scientific Journal Video about A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy at JoVE.com

A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy

Dette manuskriptet gir en detaljert totrinns kirurgisk prosedyre for å utføre musen 5/6th delvis nephrectomy (PNx) med pole hemorroider. Fire uker etter operasjonen med humbug-opererte mus, PNx musene utviklet svekket nyre-funksjon, anemi, hjerte-hypertrofi, hjerte fibrose og redusert hjertefunksjon systolisk og diastolisk.

En mus 5/6th Nephrectomy modell som induserer eksperimentell uremisk kardiomyopati

Chronic kidney disease (CKD) is a great risk factor for cardiovascular disease events and mortality, and progressively develops to the clinical phenotype ...

The overall goal of this procedure is to set up a simple mouse five-sixth partial nephrectomy model with pole ligation with a better survival rate than traditional models. This method can help answer key questions in the chronic kidney disease field about the development and potential therapeutic treatment of uremic cardiomyopathy. The main advantage of this technique is that it is an easy and consistently reproducible animal model that mimics the pathology of chronic kidney disease in human patients.Generally, individuals new to this method will struggle because of the much smaller kidneys, blood vessels, and ureters in the mouse. Begin by confirming the appropriate level of sedation by a lack of response to toe pinch and applying lubricant to the mouse's eyes. Place the mouse on a warming pad and insert a rectal thermometer to maintain the body temperature around 37 degrees Celsius during the procedure.Then, place the animal onto its right side and shave the hair over the surgical area. Remove any remaining hair with depillatory cream and disinfect the exposed skin with polyhydroxy dine solution and 70%ethanol. Align an autoclave surgical linen over the surgery site.And make an approximately one-centimeter lumbar incision through the skin and muscle tissue. Using the scalpel and forceps, separate the muscle and fascia to expose the left kidney. Then, use small blunt forceps to gently pull on the perirenal fat to extract the kidney from the abdominal cavity.Gently tease the connective tissue and adrenal gland from the superior end of the kidney towards the middle pylorus of the organ where the blood vessels enter and exit the renal tissue. Isolate the ureter around the inferior half of the kidney within the connective tissue, and gently separate the connective tissue from the kidney to ensure that the ureter is not ligated. It is essential to separate the connective tissue carefully so that the ureter is not damaged and does not bleed.Isolate the ureter around the inferior half of the kidney within the connective tissue. Then, use three zero silk suture strings to ligate the kidney approximately 0.4 centimeters from the superior portion, toward the middle of the pylorus and 0.4 centimeters from the inferior portion towards the pylorus. When tightening the sutures, apply just enough tension to compromise the blood supply to the distal portion of the kidney without causing bleeding on either side.If no bleeding is observed after two minutes, gently return the kidney to its original anatomic location, and use four zero and three zero sutures to close the muscle and skin layers respectively. Then, apply antibiotic ointment to the surgical area and house the mouse individually with a heat lamp and monitoring until sternal recumbency. Seven days after the polar ligation, expose the right kidney as just demonstrated.Use blunt forceps to clear the surrounding fat and connective tissue, and loosely place two three zero silk sutures around the renal artery and vein. Gently tease the connective tissue and adrenal gland from the superior end of the kidney towards the middle pylorus. Gently displacing the ureter from the inferior end of the tissue, untie all of the vessels together without causing bleeding.Next, move one loose ligature knot toward the abdominal aorta side, and the second loose ligature toward the kidney side. And tie off the abdominal aorta ligature with double knots. A solid knot will change the color of the right kidney.Tie off the second ligature knot with double knots, leaving spaces between the knots so the vessels can be cut, and cut the renal vessels. After removing the kidney, close the muscle and skin layers as just demonstrated. Then, dry the kidney with sterile gauze and weigh the harvested renal tissue.At four weeks post-surgery, the partial nephrectomy mice demonstrate significantly increased levels of cyctatin C, creatinine, and blood urea nitrogen in the plasma compared to sham surgery animals. Partial nephrectomy stimulated anemia is also apparent, as evidenced by the significantly lower hematocrit levels in the polar ligated animals. Cardiac hypertrophy and diastolic dysfunction in the partially nephrectomized mice are indicated by an increased heart-to-body-weight ratio and by transthoracic echocardiography analysis which reveals significant increases in the posterior and anterior wall thicknesses, the myocardial performance index, and the left ventricle mass index.Partial nephrectomy mediated cardiac fibrosis is also demonstrated by increases in type 1 collagen expression in left ventricle homogenates and left remnant kidney homogenates. Further, oxidant stress places an important role in the experimental uremic cardiomyopathy, significantly stimulating direct protein carbonylation modification of multiple proteins and proto-oncogene tyrosine-protein kinase activation in the left ventricle homogenates. Once mastered, this technique can be completed in 40 minutes if it is performed properly.While attempting this procedure, it's important to remember to check the respiration rate of the animal and to adjust the isofluranes as appropriate. Following this procedure, other experiments like comparing the effects of specific drug treatments on partial nephrectomy recovery can be performed to answer traditional questions about specific therapeutic treatments of interest. After its development, this technique paved the way for researchers in the field of chronic kidney disease to explore the pathology of and potential drug screening in uremic cardiomyopathy.After watching this video, you should have a good understanding of how to set up a partial nephrectomy model in the mouse.

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A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy

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Pluripotency and self-renewal are two defining characteristics of embryonic stem cells (ES cells). Understanding the underlying molecular mechanism will ...

An Analytical Tool that Quantifies Cellular Morphology Changes from Three-dimensional Fluorescence Images

Et analytisk verktøy som kvantifiserer Cellular Morfologi Endringer fra Tredimensjonal fluorescens bilder

The most common software analysis tools available for measuring fluorescence images are for two-dimensional (2D) data that rely on manual settings for ...

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis

Strategier for sporing Anastasis, A Cell Survival fenomen som reverserer apoptose

Anastasis (Greek for &#8220;rising to life&#8221;) refers to the recovery of dying cells. Before these cells recover, they have passed through important ...

Trans-inner Cell Mass Injection of Embryonic Stem Cells Leads to Higher Chimerism Rates

Trans-indre cellen masse injeksjon av embryonale stamceller fører til høyere Chimerism priser

In an effort to increase efficiency in the creation of genetically modified mice via ES Cell methodologies, we present an adaptation to the current ...

A Mouse Model of Intestinal Partial Obstruction

En musemodell av Intestinal delvis hindringer

Intestinal obstructions, that impede or block peristaltic movement, can be caused by abdominal adhesions and most gastrointestinal (GI) diseases including ...

Purification of Platelets from Mouse Blood

Rensing av blodplater fra mus Blood

Platelets are purified from whole blood to study their functional properties, which should be free from red blood cells (RBC), white blood cells (WBC), ...

A Laser Capture Microdissection Protocol That Yields High Quality RNA from Fresh-frozen Mouse Bones

En laser Capture Microdissection protokoll som gir høy kvalitet RNA fra fersk-frosne Mouse Bones

RNA yield and integrity are decisive for RNA analysis. However, it is often technically challenging to maintain RNA integrity throughout the entire laser ...

Mass Spectrometry Analysis to Identify Ubiquitylation of EYFP-tagged CENP-A (EYFP-CENP-A)

Mass Spectrometry Analysis to Identify Ubiquitylation of EYFP-tagged CENP-A EYFP-CENP-A

Massespektrometrianalyse for å identifisere Ubiquitylation av EYFP-merket CENP-A (EYFP-CENP-A)

Studying the structure and the dynamics of kinetochores and centromeres is important in understanding chromosomal instability (CIN) and cancer ...

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Skjelett fenotype analyse av en betinget stat3 sletting musemodell

Transgenic mouse models are powerful for understanding the critical genes controlling osteoclast differentiation and activity, and for studying mechanisms ...