从 miRNA34a/SIRT1/p53 通路介导肝细胞衰老研究脂肪性肝纤维化的分子机制与木瓜苷的干预作用

项目名称： 从 miRNA34a/SIRT1/p53 通路介导肝细胞衰老研究脂肪性肝纤维化的分子机制与木瓜苷的干预作用

项目编号： No.81473461

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： 刘朝奇

作者单位： 三峡大学

项目金额： 72万元

中文摘要： 近年来，脂肪性肝病已成为肝纤维化发生的主要原因之一，但脂肪性肝纤维化的发生机制尚未完全阐明，亦缺乏有效的干预措施。近期研究显示，衰老细胞具有分泌炎性因子活性，而miR-34a、SIRT1和p53基因表达与细胞衰老密切相关，但miR-34a/SIRT1/p53信号通路与脂肪性肝纤维化发生的相关性尚未研究；木瓜苷具有良好的抗炎活性与护肝效应，对脂肪性肝病亦有良好的防治作用，但其分子机制仍有待阐明。本项目拟在建立脂肪性肝纤维化动物模型与肝细胞衰老模型基础上，先采用免疫荧光、流式细胞术等方法研究脂肪性肝纤维化中肝细胞衰老及炎性因子分泌，再应用siRNA、基因转导等技术研究miR-34a/SIRT1/p53通路在介导肝细胞衰老中的作用，以及木瓜苷对miR-34a/SIRT1/p53通路与肝细胞衰老的干预作用，进而探讨脂肪性肝纤维化的发病新机制与木瓜苷的干预机制，为脂肪性肝纤维化的防治提供新思路。

中文关键词： 脂肪性肝纤维化；miR-34a/SIRT1/p53；信号通路；肝细胞衰老；木瓜苷

英文摘要： In recent years, fatty liver disease has become one of the main causes of liver fibrosis, but the mechanism of fatty liver fibrosis has not been fully elucidated, and also the lack of effective therapy. According to a recent study, senescent cells have secretory activity of inflammatory factors, while miR-34a, SIRT1 and P53 gene expression is closely related to senescence, but the relationship between miR-34a/SIRT1/p53 signal pathway and fatty liver fibrosis has not been studied; glucosides of Chaenomeles speciosa has good anti-inflammatory activity, hepatic protective effect, and also has good therapeutic effect on fatty liver disease, but the molecular mechanism remains to be elucidated. This project aims to establish fatty liver fibrosis animal model and hepatic senescence model, using immunofluorescence, flow cytometry technique to study in molecular mechanism of senescence and inflammatory factor in fatty liver fibrosis, and application of siRNA, gene transduction methods to research miR-34a/SIRT1/p53 pathway mediated hepatic senescence. And we will investigate the intervention effect of glucosides of Chaenomeles speciosa on miR-34a/SIRT1/p53 pathway and hepatic senescence, and explore the pathogenesis and intervention mechanism of glucosides of Chaenomeles speciosa in fatty liver fibrosis. It will provide a new area for the prevention and treatment of fatty liver fibrosis.

英文关键词： fatty liver fibrosis;miR-34a/SIRT1/p53 signaling pathway;hepatic senescence;glucosides of Chaenomeles speciosa(GCS)