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Pre-treatment with isoflurane ameliorates renal ischemic-reperfusion injury in mice.

机译:异氟烷预处理可以改善小鼠的肾脏缺血再灌注损伤。

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AIMS: Perioperative renal dysfunction is associated with a high mortality. The aim of this study was to investigate whether isoflurane preconditioning provides a protection against renal ischemic-reperfusion injury and whether hypoxia inducible factor 1 alpha (HIF-1 alpha) is responsible for the protection afforded by isoflurane in mice. MAIN METHODS: Adult male C57BL/6 mice received vehicle (PBS), scrambled siRNA or HIF-1 alpha siRNA via hydrodynamic injection through tail vein. Twenty-four hours after injection, they were exposed to 1.5% isoflurane in oxygen enriched air for 2h while controls without injection were exposed to oxygen enriched air. Twenty-four hours after gas exposure, mice were sacrificed and their kidney were harvested for western blot while other cohorts underwent renal ischemia-reperfusion injury induced by bilateral renal pedicle clamping for 25 min for renal histological or functional analysis 24h after reperfusion or by unilateral clamping for 40 min for survival rate analysis. KEY FINDINGS: Survival rate and the expression of HIF-1 alpha and erythropoietin were significantly increased while apoptosis, renal tubule score, blood plasma creatinine and urea were decreased by isoflurane preconditioning. HIF-1 alpha siRNA but not scrambled siRNA injection abrogated the protective effect of isoflurane preconditioning. SIGNIFICANCE: Our data suggested that isoflurane preconditioning provided a protection against renal ischemic-reperfusion injury which is very likely due to hypoxia inducible factor-1 alpha upregulation.
机译:目的:围手术期肾功能不全与高死亡率相关。这项研究的目的是调查异氟烷预处理是否可提供针对肾脏缺血再灌注损伤的保护作用,以及缺氧诱导因子1α(HIF-1 alpha)是否对小鼠异氟烷提供保护。主要方法:成年雄性C57BL / 6小鼠通过尾静脉流体动力注射接受媒介物(PBS),加扰的siRNA或HIF-1 alpha siRNA。注射后二十四小时,将它们暴露于1.5%的异氟烷​​在富氧空气中2小时,而未注射的对照组则暴露于富氧空气。暴露于气体后二十四小时,处死小鼠并收集其肾脏进行Western印迹,而其他队列则接受了由双侧肾蒂钳夹25分钟引起的肾脏缺血-再灌注损伤,以在再灌注后24h或通过单侧钳夹进行肾脏组织学或功能分析40分钟进行生存率分析。主要结果:异氟烷预处理可显着提高存活率以及HIF-1α和促红细胞生成素的表达,同时降低细胞凋亡,肾小管评分,血浆肌酐和尿素。 HIF-1 alpha siRNA而不是加扰的siRNA注射废除了异氟烷预处理的保护作用。意义:我们的数据表明,异氟烷预处理可防止肾脏缺血再灌注损伤,这很可能是由于缺氧诱导因子-1α上调引起的。

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