基于p38MAPK信号通路的解毒化浊祛瘀方对铜负荷大鼠肝星状细胞凋亡干预的代谢组学研究

项目名称： 基于p38MAPK信号通路的解毒化浊祛瘀方对铜负荷大鼠肝星状细胞凋亡干预的代谢组学研究

项目编号： No.81202692

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 张娟

作者单位： 安徽中医药大学

项目金额： 23万元

中文摘要： 肝豆状核变性(Wilson disease,WD)是常染色体隐性遗传铜代谢障碍性疾病，肝脏是WD最先受累的脏器之一，肝纤维化几乎是每个WD患者肝脏主要病理改变。研究证明：肝纤维化是可以逆转的，以HSC为靶标、干扰细胞信号通路等途径治疗肝纤维化，是目前研究的热点，代谢组学亦是中药整体药效评价的有力工具。课题组依据WD肝纤维化铜毒内蕴、痰瘀阻络的病机及现代医学原理提出：解毒化浊祛瘀方肝豆汤可能通过p38MAPK信号通路诱导HSC凋亡、影响肝组织小分子代谢物的变化而逆转WD肝纤维化。本课题拟在前期工作基础上开展以下研究：以p38MAPK 信号转导通路、代谢组学为切入点，初步探讨解毒化浊祛瘀方对铜负荷大鼠肝纤维化HSC信号通路的干预作用，以期发现该方对WD肝纤维化的作用靶点，为解毒化浊祛瘀方治疗WD肝纤维化建立分子生物学基础。

中文关键词： 肝豆状核变性；铜负荷大鼠；肝星状细胞；p38MAPK信号通路；代谢组学

英文摘要： Wilson disease is an autosomal recessive disorder of copper homeostasis, liver is the first organ involved in, hepatic fibrosis is the main liver pathological change almost in every WD patients. Research shows:hepatic fibrosis is reversible，it is the hot spot of treatment to hepatic fibrosis by taking HSC as targets and interfering with the way such as cell signaling pathways at present，metabolomics is also a powerful tool of overall efficacy evaluation of traditional Chinese medicine.According to the pathogenesis of copper poison deposition,stagna- tion of phlegm and blood and principles of modern medicine,our research group put forward the following points:the detoxification resolving turbidity and expelling stasis recipe probably reverse hepatic fibrosis in WD through p38MAPK signal pathway to induce apoptosis of HSC, probably affect the change of small molecules metabolites of liver tissue. This topic carry out the following research based on the previous work: taking p38MAPK signalling pathway and metabolomics as the breakthrough point, to preliminary discuss the intervention role of the detoxification resolving turbi- dity and expelling stasis recipe to HSC signalling pathway of hepatic fibrosis in copper overload rats. In order to find the acting targets of the recipe for hepatic fibrosis in WD，to establ

英文关键词： WD；copper overload rats；HSC；p38MAPK；Metabonomics