黄芪汤和茵陈蒿汤改善大鼠肝纤维化的效果及分子机制--差异基因表达谱的比较分析  

Effects and Molecular Mechanism of Huangqi Decoction and Yinchenhao Decoction on Liver Fibrosis in Rats: A Comparative Analysis of Differential Gene Expression Profile

作　　者：张贵彪[1] 宋雅楠[1] 董姝[1] 陆奕宇[1] 孙明瑜[2] 刘平[3] 苏式兵[1] 

机构地区：[1]上海中医药大学复杂系统研究中心,上海中医药大学,上海201203 [2]上海中医药大学附属曙光医院肝病研究所,上海201203 [3]上海中医药大学E研究院,上海201203

出　　处：《中华中医药学刊》2015年第9期2103-2108,I0005,共7页Chinese Archives of Traditional Chinese Medicine

基　　金：国家科技重大专项(2009ZX09311-003);上海市科委重点项目(12401900401);上海市教委E研究院建设项目(E03008)

摘　　要：目的:探讨黄芪汤和茵陈蒿汤抑制二甲基亚硝胺(DMN)诱导的大鼠肝纤维化中对信号传导通路调节的差异。方法:大鼠被随机分为正常组、黄芪汤组、茵陈蒿汤组和模型组,并予以DMN造模及相应药物治疗。观察各组肝组织病理学变化和羟脯氨酸含量;采用全基因组芯片检测,进行差异基因,富集功能GOs及信号通路分析。结果:与正常组相比,模型组出现显著的肝损伤和肝纤维化,肝组织羟脯氨酸(Hyp)含量显著升高(P<0.01)。与模型组比较,黄芪汤和茵陈蒿汤均显著改善肝组织病理,降低Hyp含量(P<0.01)。黄芪汤、茵陈蒿汤与模型组比较的差异基因分别为373个和432个,共有基因189个。各用药组都作用于Notch介导的上皮间质转化(EMT)通路、Notch和细胞粘附细胞基质糖复合物通路。黄芪汤还作用于血管内皮生长因子与促血管生成素通路、血小板反应素通路等;茵陈蒿汤还作用于细胞黏附-细胞外基质重塑通路、EMT通路等。结论:黄芪汤和茵陈蒿汤都能显著抑制DMN诱导的大鼠肝纤维化。黄芪汤益气扶正的功效主要与调节Notch诱导的EMT信号通路相关,茵陈蒿汤清热利湿的祛邪作用侧重于调节细胞黏附-细胞外基质(ECM)信号通路。Objective： To investigate the effects and molecular mechanism of Huangqi Decoction（HQD） and Yinchenhao Decoction（YCHD） on the liver fibrosis in rats through the comparative analysis of differential gene expression profiles and signaling pathways. Methods： DMN induced liver fibrosis model in rats were randomly divided into normal group,HQD group,YCHD group and model group,treated by HQD or YCHD. The pathological changes of hepatic tissue were observed and hydroxyproline（Hyp） contents were measured. The gene expression profile was detected by whole genome chip testing and the differentiated expressed genes（DEGs）,gene ontology（GO） and signal pathways were analyzed. Results： Compared to normal group,model group presented the pathological changes of liver damage and liver fibrosis and the Hyp content of liver tissue significantly increased（P〈 0. 01）. Compared to model group,in HQD and YCHD group,the pathological changes were markedly improved of liver tissue and collagen hyperplasia degree and Hyp contents were significantly reduced（P〈 0. 01） and the effects in YCHD was slightly better than in HQD. Compared to model group,the DEGs of HQD and YCHD were 373 and 432,including 189 co-own gene. Both of treatment group acted on Notch and Notch-induced EMT signaling pathway,and cell adhesion,cell matrix glycoconjugates pathway. HQD group still acted on VEGF and angiopoietin pathways,thrombospondin pathway and so on. YCHD group still acted on cell adhesion-ECM remodeling pathway,EMT regulation pathway and so on. Conclusion HQD and YCHD significantly improved liver fibrosis induced by DMN in rats. There were similarities and differences in their gene expressions and signaling pathways.Strengthening the body resistance of HQD is mainly related to adjusting Notch-induced EMT signaling pathway and eliminating pathogenic effects of YCHD is mostly regulated by cell adhesion-ECM pathway.

关 键 词：黄芪汤 茵陈蒿汤 肝纤维化 差异基因 信号通路 

分 类 号：R285.5[医药卫生—中药学]