A new mouse model of hemorrhagic shock-induced acute kidney injury.
A new mouse model of hemorrhagic shock-induced acute kidney injury.
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DOI：
10.1152/ajprenal.00347.2016
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发表时间：
2017
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影响因子：
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通讯作者：
Lei Wang;Jiang-ping Song;J. Buggs;Jin Wei;Shaohui Wang;Jie Zhang;Gensheng Zhang;Yan Lu;K. Yip;Ruisheng Liu
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文献类型：
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作者：
Lei Wang;Jiang-ping Song;J. Buggs;Jin Wei;Shaohui Wang;Jie Zhang;Gensheng Zhang;Yan Lu;K. Yip;Ruisheng Liu
目前失血性休克所致急性肾损伤(HS-Induced AKI)的动物模型需要广泛的外科手术和持续监测血流动力学参数。将这些HS诱导的AKI模型应用于小鼠以产生一致的肾脏损伤是具有挑战性的。在本研究中，我们通过适度出血和肾蒂夹闭相结合的方法建立了一种简单、重复性好的HS诱导的AKI小鼠模型，简称HS-AKI。用C57BL/6小鼠眶后出血0.4ml建立HS模型。将小鼠置于HS阶段30min，然后在36.8~37.0℃的温度下夹闭肾蒂18min，在整个实验过程中使用预先植入的无线电发射器监测平均动脉压(MAP)和心率。用跨音速血流探头检测HS引起的急性肾血流反应(RBF)。小鼠接受假手术；单独出血和单独夹闭肾蒂作为对照。出血后MAP由77±4降至35±3 mm Hg。在HS期间，RBF减少了65%。再灌流24 h后，血浆肌酐和肾脏损伤分子-1水平均升高22倍以上。再灌流3d后，GFR下降78%。组织学检查显示中至重度急性肾小管损伤，主要发生在皮质-髓质交界区，其次是髓质和皮质区域。HS单独应用未引起明显的肾损伤，但协同作用增强了椎弓根夹闭所致的AKI。这是一种控制良好、简单可靠的HS-AKI小鼠模型。
Current animal models of hemorrhagic shock-induced acute kidney injury (HS-induced AKI) require extensive surgical procedures and constant monitoring of hemodynamic parameters. Application of these HS-induced AKI models in mice to produce consistent kidney injury is challenging. In the present study, we developed a simple and highly reproducible mouse model of HS-induced AKI by combining moderate bleeding and renal pedicle clamping, which was abbreviated as HS-AKI. HS was induced by retroorbital bleeding of 0.4 ml blood in C57BL/6 mice. Mice were left in HS stage for 30 min, followed by renal pedicle clamping for 18 min at 36.8-37.0°C. Mean arterial pressure (MAP) and heart rate were monitored with preimplanted radio transmitters throughout the experiment. The acute response in renal blood flow (RBF) triggered by HS was measured with transonic flow probe. Mice received sham operation; bleeding alone and renal pedicle clamping alone served as respective controls. MAP was reduced from 77 ± 4 to 35 ± 3 mmHg after bleeding. RBF was reduced by 65% in the HS period. Plasma creatinine and kidney injury molecule-1 levels were increased by more than 22-fold 24 h after reperfusion. GFR was declined by 78% of baseline 3 days after reperfusion. Histological examination revealed a moderate-to-severe acute tubular damage, mostly at the cortex-medulla junction area, followed by the medullar and cortex regions. HS alone did not induce significant kidney injury, but synergistically enhanced pedicle clamping-induced AKI. This is a well-controlled, simple, and reliable mouse model of HS-AKI.