基于CCl_4诱导大鼠纤维化肝组织microRNA差异表达分析加减三甲散改善大鼠肝纤维化的分子机制  

Molecular mechanism of Modified Sanjia Powder improving hepatic fibrosis through differential expression of micro RNA in liver tissue of rats induced by CCl_4

作　　者：刘业方 张传涛[3] 郭尹玲[1] 李白雪[1] 王宝家[1] 王政[1] 舒发明 罗雪梅[1] 杨宇[1] 

机构地区：[1]成都中医药大学,成都610075 [2]郫县中医院,成都611730 [3]成都中医药大学附属医院,成都610072

出　　处：《中华中医药杂志》2016年第7期2530-2534,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81503569;No.81202624;No.81102720);教育部博士点基金项目(No.20125132120011);四川省教育厅科研项目(No.132B0321)~~

摘　　要：目的:研究加减三甲散对四氯化碳(CCl_4)诱导的肝纤维化大鼠模型microRNAs的影响,从基因水平探索该方抗肝纤维化的分子机制。方法:采用micro RNA高通量测序技术检测正常组、模型组与加减三甲散组肝组织microRNAs表达;取正常较模型组差异miro RNAs与模型组较加减三甲散组差异miro RNAs的交集进行靶基因预测,对靶基因进行GO分析和Pathway分析。结果:正常较模型组、模型组较加减三甲散组差异miro RNAs的交集中,筛选出14个差异micro RNAs;GO分析和Pathway分析提示,差异micro RNAs调控细胞内有机/无机物质的应答,细胞化学平衡、抗凋亡作用、积极的调节蛋白激酶活性、脂肪酸代谢过程等;显著信号转导通路主要包括钙信号通路、PPAR信号通路,Wnt信号通路、MAPK信号通路,凋亡,TGF-β信号通路等。结论:加减三甲散通过调控多个miro RNAs,进而调控多个生物学功能和多个信号转导通路进行抗肝纤维化治疗。Objective： To study the effect of Modified Sanjia Powder on differential expression of micro RNA in liver tissue in hepatic fibrosis rat induced by carbon tetrachloride（CCl_4）, and to explore its molecular mechanism. Methods： The liver tissue expression of micro RNAs of normal group, model group and Modified Sanjia Powder group were detected by highthroughput sequencing. Gene ontology（GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） Pathway analysis of the targets of intersection of micro RNAs between normal and model group, and model and Modified Sanjia Powder group were carried out in this study. Results： Fourteen differentally expressed micro RNAs were identified in the intersection between normal and model group, and model and Modified Sanjia Powder group; GO analysis and Pathway analysis showed that differential micro RNAs regulating organic/inorganic qualitative of cell response, cell chemical equilibrium, antiapoptotic effect, positive regulation of protein kinase activity and fatty acid metabolism; the remarkable signaling pathway including calcium signaling pathways, PPAR signaling pathways, Wnt signaling pathway and MAPK signal pathway, apoptosis, TGF-β signaling pathways, etc. Conclusion： Modified Sanjia Powder improves the pathological changes of hepatic fibrosis through the regulation of miro RNAs of the regulation of multiple genes and multiple signal pathways.

关 键 词：加减三甲散 微小RNA 肝纤维化 差异表达 

分 类 号：R285.5[医药卫生—中药学]