基于自噬途径探讨肝纤维化细胞上皮间质转化现象的分子机制及扶脾柔肝方的干预研究

项目名称： 基于自噬途径探讨肝纤维化细胞上皮间质转化现象的分子机制及扶脾柔肝方的干预研究

项目编号： No.81460726

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： 安祯祥

作者单位： 贵州中医药大学

项目金额： 47万元

中文摘要： 肝纤维化(HF)是慢性肝病向肝硬化发展的必经中间环节，其中心环节在于肝星状细胞(HSC)的激活。自噬通过降解脂滴为HSC活化提供能量，促进HF的发生。HSC活化通过上皮间质转化（EMT）获得成纤维细胞的表型,转变为肌成纤维细胞(MFB),促进HF的发生与发展。本研究基于见肝之病，知肝传脾，当先实脾的实脾理论，从自噬-能量代谢-EMT的环节探讨HF的分子机制及中药扶脾柔肝方对HF干预的效应机制。通过建立HF动物模型及EMT细胞模型，对自噬通路的调控，检测自噬PI3K/Akt/mTOR通路、EMT TGF-β/Smads/Snail通路中关键的信号传导分子Akt、mTOR、Beclin 1、LC3-Ⅱ、TGF-β1、Smad3、Snail、E-cadherin、a-SMA、AMPK的表达情况，探讨自噬与EMT的协同作用，为揭示中医实脾理论及扶脾柔肝方治疗HF的作用机制提供依据。

中文关键词： 肝纤维化；扶脾柔肝方；自噬；上皮间质转化

英文摘要： HHepatic fibrosis (HF) is a necessary intermediate link in the process which chronic hepatopathy evolves to liver cirrhosis, and the inducing factor of HF lies in hepatic stellate cell(HSC) activation. Autophagy is a vacuolar process of cytoplasmic degradation by lysosome.) which can yield the energy for the activation of HSC and accelerate the occurrence of HF. In other words, the activation of HSC, the fibroblast phenotype from the epithelial mesenchymal transition(EMT) was gradually transformed into the myofibroblasts (MFB), and finally caused the occurrence and development of HF. This research is based on theory of nourishing spleen, which means that when partial liver disease occurs, it will spread to the whole liver;therefore we should nourish the spleen before treating the liver ; moreover. It is from the autophagy of HSC -and EMT-energy metabolism link that so much are learned about the pathophysiological mechanism of HF and the action or effects of traditional Chinese medicine Tonifying Spleen and Liver(TSL) on HF , Through the establishment of HF animal and EMT cell model ,and the regulation of autophagy pathway, expression of key signal transduction molecules of Akt, mTOR, Beclin 1, LC3- Ⅱ, TGF- β 1, Smad3, Snail, E-cadherin, a-SMA, AMPK in PI3K/Akt/mTOR pathway and EMT TGF- β /Smads/Snail pathway,and the probe on synergistic effect of autophagy and EMT, it is aimed to provide experimental basis for Traditional Chinese Medicine (TCM)theory of Nourishing Spleen Method and the effective mechanism of TSL powder in the treatment of HF.

英文关键词： Hepatic Fibrosis;Fu pi rou gan Powder;autophagy;EMT