高压氧对小鼠缺血再灌注肾组织自噬的影响及机制研究

项目名称： 高压氧对小鼠缺血再灌注肾组织自噬的影响及机制研究

项目编号： No.81460135

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 梁国标

作者单位： 遵义医科大学

项目金额： 47万元

中文摘要： 肾缺血再灌注（IR）损伤是急性肾损伤（AKI）的一个常见原因，而AKI是肾功能衰竭的主要原因之一。自噬是细胞内的重要降解系统，在多种病理和生理情况下发挥重要作用，自噬也参与了IR损伤的发生发展。自噬是肾小管细胞维持稳态的重要机制，可能通过多种不同的信号通路在肾IR损伤中发挥作用，但关于其作用的研究观点尚存在明显不同，其确切机制也未完全阐明。研究显示高压氧（HBO）治疗能明显减轻肾IR损伤。最近本课题组初步研究发现IR后HBO治疗能明显增强肾组织自噬，然而，自噬在肾IR中究竟扮演何种角色，HBO治疗究竟是否通过调节自噬以及如何调节并不清楚。因此，本项目拟采用小鼠自噬基因敲除和自噬诱导两种方法研究自噬在肾IR损伤中的作用，并探讨HBO治疗对自噬及其信号通路的影响；试图进一步阐明自噬在肾IR损伤中的作用和机制，以及HBO治疗对自噬的调控机制，以期为临床肾IR损伤的防治提供新的理论依据及新策略。

中文关键词： 高压氧；急性肾损伤；缺血再灌注损伤；自噬；肾小管上皮细胞

英文摘要： Renal ischemia-reperfusion (IR) injury is a main cause of acute kidney injury(AKI) , and AKI is one of the major causes of renal failure.Autophagy is an important intracellular degradation system. As is well known, autophagy plays an important role in various pathological and physiological events, including development of IR injury. Autophagy is an essential mechanism for maintaining homeostasis of renal tubular cell, and it may be involved in renal IR injury through various signal pathways with obvious difference in research point, and the precise mechanism of action of autophagy in renal IR injury is not still clarified. It is demonstrated that hyperbaric oxygenation (HBO) therapy significantly attenuated renal IR injury. Recently, we initially found HBO therapy significantly augmented renal autophagy after IR injury. However, it is not clear that the exact role of autophagy in renal IR injury and whether and how HBO therapy regulates autophagy. In this present study, the role of autophagy and its signal pathways in renal IR injury in mouse will be investigated by two methods of autophagic gene knockout and induction, and the influence of HBO on autophagy will also be explored. Therefore, the aim of this study is to further clarify the role and mechanism of autophagy in renal IR injury and the regulatory mechanism to autophagy by HBO therapy, so as to provide new theory and new strategy for clinic prevention of renal IR injury.

英文关键词： hyperbaric oxygenation;acute kidney injury;ischemia reperfusion injury;autophagy;renal tubular epithelial cell