项目名称: 间充质干细胞强化肝细胞自噬治疗急性肝功能衰竭的作用及机制研究
项目编号: No.81500478
项目类型: 青年科学基金项目
立项/批准年度: 2016
项目学科: 医药、卫生
项目作者: 马虎成
作者单位: 南京大学
项目金额: 18万元
中文摘要: 既往研究证实MSCs治疗ALF是一种有效的方式,有望替代肝移植成为治疗ALF新手段。但MSCs治疗ALF的主要机理仍存有争议。目前发现细胞自噬存在于大量病理过程中,对维持细胞内稳态具有重要作用。但目前尚没有研究探索ALF中MSCs对肝细胞自噬的调节作用。本课题在之前研究的基础上,结合国内外最新研究成果,创新性提出:MSCs通过上调Beclin1促进损伤肝细胞发生自噬进而减轻肝损伤可能是MSCs移植治疗ALF的新机制。为证实以上假设,本研究拟:明确MSCs移植对ALF的治疗作用,并探索自噬与肝损伤的关系;探索MSCs是否能够强化损伤肝细胞的自噬;构建自噬相关蛋白芯片,筛选MSCs调节损伤肝细胞自噬的关键蛋白;构建Beclin1 shRNA,探索Beclin1在MSCs调节损伤肝细胞自噬中的作用。本项目的顺利完成将丰富MSCs移植治疗ALF的机理,为ALF的治疗提供更广阔的应用途径。
中文关键词: 间充质干细胞;细胞移植;自噬;急性肝功能衰竭
英文摘要: Mesenchymal stem cells (MSCs) transplantation has been proven to be an effective therapy for acute liver failure (ALF), expected to become an alternative way instead of liver transplantation for ALF. But the major mechanism of MSCs transplantation for ALF remains controversial. Autophagy exists in many pathological processes and plays an important role play in the maintenance of intracellular homeostasis. By now, no research aims to explore the regulation effect of MSCs on hepatocytes autophagy in ALF. Based on our prior research and combined with the latest opinions, the applicant proposed: Regulating autophagy by Beclin 1 is the main mechanism of MSCs transplantation for ALF. In order to prove this hypothesis, this study intends to do the following research: to explore the therapeutic effect of MSCs transplantation for ALF and the relationship between autophagy and liver injury; to explore whether MSCs can enhance autophagy of damaged hepatocytes; to explore the key protein involving in autophagy modulation; to construct Beclin1 shRNA and explore the role of Beclin1. The successful completion of this project will enrich the mechanism of MSCs transplantation in the treatment of ALF and provide a broader application of the treatment approach for ALF.
英文关键词: mesenchymal stem cells ;cell transplantation;autophagy ;acute liver failure