莪术醇干预肝纤维化HSEC及其信号调控作用的研究

项目名称： 莪术醇干预肝纤维化HSEC及其信号调控作用的研究

项目编号： No.81460628

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： 赵铁建

作者单位： 广西中医药大学

项目金额： 47万元

中文摘要： 肝纤维化是各种慢性肝病向肝硬化发展必经过程。前期研究发现广西莪术提取物莪术醇可促进HSC凋亡和抑制其分泌，还可通过影响HSEC结构与分泌功能呈现抗肝纤维化作用。提出肝纤维化与HSC、HSEC 超微结构和分泌功能改变有关，莪术醇通过干预HSEC超微结构和分泌功能参与肝纤维化逆转观点。拟建立肝纤维化模型和HSEC模型，通过免疫荧光、western blot、定量PCR、电镜技术等方法，选择ET-1、VEGF、CTGF、uPA/ uPAR、Perlecan、RhoA、Cdc42、Rac1等因子和HSEC超微结构等指标，观察HSEC结构与功能改变、Rho-GTPase信号通路及HSEC和HSC之间调节的影响，明确莪术醇干预肝纤维化作用环节及其靶位点，并从莪术醇对Rho-GTPase信号通路的相关分子表达水平阐明血瘀症肝纤维化形成和莪术醇干预肝纤维化的分子机制。为莪术醇开发利用提供更多科学依据。

中文关键词： 莪术醇；抗肝纤维化；肝窦内皮细胞；信号通路；作用机制

英文摘要： Liver fibrosis is a necessary process of a variety of chronic liver diseases to cirrhosis. Our previous study found that extracts of Curcumol can not only promote HSC apoptosis and inhibit secretion of many factors, but also present the function of anti-hepatic fibrosis by influencing the structure and secretion of HSEC. Basing on our view that changes in the ultrastructure and secretion of HSC, HSEC are related to liver fibrosis, and extracts of Curcumol can intervene ultra-structure and secretion of HSEC in hepatic fibrosis. In the study, build animal models of liver fibrosis and HSEC model, detect ET-1, VEGF, CTGF, uPA / uPAR, Perlecan, RhoA, Cdc42, Rac1 and other factors and other indicators by western blot, quantitative PCR, electron microscopy, et al, HSEC ultrastructure will be observed by the methods of immunofluorescence. We aim to clear the targeting site to liver cirrhosis by extracts of Curcumol in the molecular level of the Rho-GTPase signaling pathway so as to provide basis for further use and research of the extracts of Curcumol.

英文关键词： Curcumol;anit-liver fibrosis;hepatic sinusoidal endothelial cell;signaling pathway;mechanism of action