Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice

被引:121
作者
Skrypnyk, Nataliya I. [1 ]
Harris, Raymond C. [1 ]
de Caestecker, Mark P. [1 ]
机构
[1] Vanderbilt Univ, Med Ctr, Div Nephrol, Nashville, TN 37235 USA
来源
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS | 2013年 / 78期
关键词
Medicine; Issue; 78; Immunology; Infection; Biomedical Engineering; Anatomy; Physiology; Kidney; Mice; Inbred Strains; Renal Insufficiency; Acute Kidney Injury; Ischemia-reperfusion; acute kidney injury; post injury fibrosis; mice; ischemia; reperfusion; fibrosis; animal model; ACUTE-RENAL-FAILURE; CREATININE; RATS;
D O I
10.3791/50495
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Ischemia-reperfusion induced acute kidney injury (IR-AKI) is widely used as a model of AKI in mice, but results are often quite variable with high, often unreported mortality rates that may confound analyses. Bilateral renal pedicle clamping is commonly used to induce IR-AKI, but differences between effective clamp pressures and/or renal responses to ischemia between kidneys often lead to more variable results. In addition, shorter clamp times are known to induce more variable tubular injury, and while mice undergoing bilateral injury with longer clamp times develop more consistent tubular injury, they often die within the first 3 days after injury due to severe renal insufficiency. To improve post-injury survival and obtain more consistent and predictable results, we have developed two models of unilateral ischemia-reperfusion injury followed by contralateral nephrectomy. Both surgeries are performed using a dorsal approach, reducing surgical stress resulting from ventral laparotomy, commonly used for mouse IR-AKI surgeries. For induction of moderate injury BALB/c mice undergo unilateral clamping of the renal pedicle for 26 min and also undergo simultaneous contralateral nephrectomy. Using this approach, 50-60% of mice develop moderate AKI 24 hr after injury but 90-100% of mice survive. To induce more severe AKI, BALB/c mice undergo renal pedicle clamping for 30 min followed by contralateral nephrectomy 8 days after injury. This allows functional assessment of renal recovery after injury with 90-100% survival. Early post-injury tubular damage as well as post injury fibrosis are highly consistent using this model.
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页数:6
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