Ischemia-reperfusion model of acute kidney injury and post injury fibrosis in mice.
Ischemia-reperfusion model of acute kidney injury and post injury fibrosis in mice.
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DOI：
10.3791/50495
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发表时间：
2013-08-09
期刊：
影响因子：
--
通讯作者：
de Caestecker MP
中科院分区：
文献类型：
--
作者：
Skrypnyk NI;Harris RC;de Caestecker MP
缺血-再灌注诱导的急性肾损伤（IR-AKI）被广泛用作小鼠阿基模型，但结果往往差异很大，死亡率很高，通常未报告，可能会混淆分析。双侧肾蒂钳夹常用于诱导IR-AKI，但有效钳夹压力和/或肾脏对肾脏间缺血的反应之间的差异通常导致更多可变结果。此外，已知较短的钳夹时间会诱导更多可变的肾小管损伤，而经受双侧损伤且钳夹时间较长的小鼠会产生更一致的肾小管损伤，它们通常在损伤后前3天内因严重肾功能不全而死亡。为了提高损伤后的存活率，并获得更一致和可预测的结果，我们已经开发了两种模型，单侧缺血再灌注损伤，然后对侧肾切除。两种手术均使用背侧入路进行，减少了腹侧剖腹术（通常用于小鼠IR-AKI手术）引起的手术应力。对于中度损伤的诱导，BALB/c小鼠经历单侧肾蒂夹紧26分钟，并且还经历同时的对侧肾切除术。使用这种方法，50-60%的小鼠在损伤后24小时发生中度阿基，但90-100%的小鼠存活。为了诱导更严重的阿基，BALB/c小鼠在损伤后8天经历肾蒂夹闭30分钟，随后进行对侧肾切除术。这允许在90-100%的存活率下对损伤后的肾恢复进行功能评估。使用该模型，早期损伤后肾小管损伤以及损伤后纤维化高度一致。
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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影响因子：
19.6
作者：
Dunn, SR;Qi, ZH;Sharma, K
通讯作者：
Sharma, K
DOI：
10.1007/978-1-61779-851-1_32
发表时间：
2012-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Oxburgh, Leif;de Caestecker, Mark P
通讯作者：
de Caestecker, Mark P
影响因子：
19.6
作者：
通讯作者：
--
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
19.6
作者：
Keppler, A.;Gretz, N.;Pill, J.
通讯作者：
Pill, J.