项目名称： 氙气预适应通过miR-21调控机制预防脓毒症急性肾损伤的实验研究

项目编号： No.81471890

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 贾平

作者单位： 复旦大学

项目金额： 72万元

中文摘要： 急性肾损伤（AKI）是严重威胁人类健康的常见危重病，是危重病救治的重要领域。其中脓毒症引起者占50%，且死亡率极高，是AKI防治的难点。细胞凋亡、炎症反应是脓毒症性AKI的重要病理生理机制。miR-21是调控凋亡和免疫炎症的重要基因。申请人前期研究发现，氙气预适应通过上调肾脏miR-21表达，抑制细胞凋亡，减轻药物性、缺血性肾损伤。因而推测氙气预适应也可能通过miR-21干预脓毒症AKI的发生发展。预实验亦初步证实氙气能够减轻脂多糖诱发的小鼠肾损伤，但具体作用机制尚不清楚。本项目在前期研究基础上，拟采用脂多糖诱导miR-21转基因小鼠和野生鼠AKI模型，从抗凋亡、抗炎等方面深入探讨氙气预适应对脓毒症AKI的防治作用；并利用生物信息学、锁核苷酸修饰及RNA干扰等技术深入阐明miR-21及其下游信号通路在氙气预适应机制中的作用，从而为脓毒症AKI的防治提供新的靶点和思路。

中文关键词： 急性肾损伤；脂多糖；氙气；微小RNA

英文摘要： As a common critical disease, acute kidney injury (AKI) is a serious threat to human health, and an important field of critical care medicine. AKI induced by sepsis (septic AKI) accounts for 50% of the overall incidence of AKI, with high mortality and poor prognosis, and is still lack of effective prevention and treatments. Cell apoptosis and inflammation are important pathophysiological mechanisms of septic AKI. MiR-21 is an important gene in regulating apoptosis and inflammation. In our previous studies, we found that xenon preconditioning protected from ischemic renal injury and nephrotoxicity by upregulating miR-21 in the kidney and inhibitting apoptosis. Thus, we speculate that xenon preconditioning may also prevent septic AKI. Preliminary experiment showed that xenon reduced renal damage induced by lipopolysaccharide (LPS) in mice, but its mechanism is still not clear. In this study, with the acute kidney injury model induced by LPS in miR-21 transgenic mice and wild mice, we further explore the protective effects of xenon on apoptosis and inflammation, and elucidate the potential mechanisms underlying xenon preconditioning with bioinformatics, lock nucleotide modification and RNA interference technology. This study not only extends the research of xenon as a potential organ protective agent in the prevention and treatment of AKI, but also provides a new target for the prevention of septic AKI.

英文关键词： acute kidney injury;lipopolysaccharide;xenon;microRNA