Morphologic and functional renal impact of acute kidney injury after prolonged hemorrhagic shock in mice
Morphologic and functional renal impact of acute kidney injury after prolonged hemorrhagic shock in mice
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DOI：
10.1097/ccm.0b013e31821f04f0
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发表时间：
2011-09-01
影响因子：
8.8
通讯作者：
Tack, Ivan
中科院分区：
文献类型：
--
作者：
Mayeur, Nicolas;Minville, Vincent;Tack, Ivan
目的：关于小鼠失血性休克的肾脏后果的数据很少。本研究的目的是扩大目前的知识对失血性休克小鼠的肾功能和形态的影响，并确定其作为一个准确的急性肾损伤模型的能力。设计：在体内研究。设置：大学研究单位。主题：C57/B16小鼠。干预措施：采用控制性失血性休克模型来确定失血性休克对小鼠肾脏的影响。测量和主要结果：失血性休克后3小时至21天随访肾功能和肾脏形态。当延长至2小时，低血压（35毫米汞柱的平均动脉血压）引起的暂时性血液去除是负责早期和持久的增加缺氧诱导因子-1 α和肾诱导分子-1基因表达，急性肾小管坏死和肾功能衰竭。失血性休克后6天，2小时低血压可引起肾小球滤过率显著但可逆的降低。其他肾功能障碍包括肾钠丢失（通过钠排泄增加评估）和持续至第21天的尿浓度降低。失血性休克后2天，外髓质组织损伤占主导地位，在第6天达到最大。在第21天，肾愈合与上皮恢复和一个显着的间质fibrosis.Conclusions：我们的数据表明，急性肾损伤后肾功能的明显恢复可以掩盖持续的功能障碍和组织损伤，可能易患慢性肾脏疾病。小鼠的长期失血性休克与人类类似情况下引起的肾脏效应非常相似，因此为研究失血性休克等情况下急性肾损伤的病理生理机制和保护策略提供了有用的工具。(Crit Care Med 2011; 39：2131-2138）
Objective: Sparse data are available on renal consequences of hemorrhagic shock in mice. This study aimed to extend the current knowledge on functional and morphologic renal impact of hemorrhagic shock in mice and to determine its ability to stand as an accurate model of acute kidney injury.Design: In vivo study.Setting: University research unit. Subjects: C57/Bl6 mice.Interventions: A model of controlled hemorrhagic shock was adapted to determine the renal impact of hemorrhagic shock in mice.Measurements and Main Results: Renal functions and kidney morphology were followed up from 3 hrs to 21 days after hemorrhagic shock. When prolonged up to 2 hrs, hypotension (35 mm Hg mean arterial blood pressure) induced by temporary blood removal was responsible for an early and lasting increase in hypoxia-inducible factor-1 alpha and kidney-inducible molecule-1 gene expression that paralleled acute tubular necrosis and renal failure. Two-hr hypotension induced an important but reversible decrease in glomerular filtration rate up to 6 days after hemorrhagic shock. Other renal dysfunctions included a renal loss of sodium, assessed by the increase in sodium excretion, and a decrease in urine concentration that persists up to day 21. Tissular damages prevailed in the outer medulla 2 days after hemorrhagic shock, being maximal at day 6. At day 21, renal healing was associated with epithelial recovery and a significant interstitial fibrosis.Conclusions: Our data indicate that apparent recovery of renal function after acute kidney injury can mask persisting dysfunctions and tissular damages that could predispose to chronic kidney disease. Prolonged hemorrhagic shock in mice closely mimics renal effects induced by similar situation in humans, thus providing a useful tool to investigate pathophysiological mechanisms and protection strategies against acute kidney injury in situations such as hemorrhagic shock. (Crit Care Med 2011; 39: 2131-2138)