Insulin/Glucose调控的H2O2信号在肝再生调控中的作用及机制研究

项目名称： Insulin/Glucose调控的H2O2信号在肝再生调控中的作用及机制研究

项目编号： No.31200635

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 柏桦

作者单位： 中国人民解放军第四军医大学

项目金额： 23万元

中文摘要： 肝细胞通过调节自身增殖、静息状态的转变参与肝损伤后再生修复、癌变等重要过程，然而调控肝再生启动、终止的具体信号机制尚不清楚。本项目抓住肝切除后正常肝再生过程中Insulin、Glucose、H2O2、肝增殖水平、氧化-抗氧化水平的内在变化规律与联系，将H2O2信号强度与肝再生中肝细胞增殖状态的转变有机联系起来，提出了"Insulin/Glucose发挥H2O2产生、清除的双向调节作用，使H2O2在肝再生不同阶段达到不同水平的动态平衡，进而选择性有序激活AKT/Erk/p38通路、调控细胞周期"这一新的设想。本项目拟采用原代肝细胞模型、单纯肝切除模型及不同因素导致的肝再生抑制模型等手段，明确H2O2参与肝再生调控的关键作用及剂量依赖性调控机制，阐明Insulin、Glucose在H2O2水平调控中的作用及调控途径，为临床有效促进、合理调控肝再生提供实验依据和治疗线索。

中文关键词： 过氧化氢；肝再生；细胞周期；；

英文摘要： Hepatocytes transition between proliferation and quiescence are involved in many important physiological or pathological processes such as injury caused liver regeneration and repair and even cancer. However, the exact mechanisms that regulate the priming and cessation of liver regeneration are still remained to be explained.In this project,relying on the time-dependent changes of insulin,glucose,H2O2,proliferating viability and redox state during liver regeneration, we proposed that insulin/glucose play dual roles in producing and scavenging H2O2 to control it in different levels during different phases in liver regeneration, so as to activate Akt/Erk/p38 pathways dose-dependently and finally regulate cell cycle progress.We employ the primary hepatocytes,hepatectomy and inhibited liver regeneration models to prove that H2O2 play critical signaling roles in liver regeneration and explain the dose-dependent regulating mechanisms. Furtherly, whether and how insulin and glucose are invovled in H2O2 level control will also be clarified. Our research may provide the basis for the development of new strategies to improve regeneration in patients with acute or chronic liver damage.

英文关键词： hydrogen peroxide；liver regeneration；cell cycle；；