基于PI3K/AKT和MAPK信号通路探讨防风桃红四物汤抗肝纤维化的作用机制

A study on the mechanism of the Fangfeng Taohong Siwu decoction on anti-hepatic fibrosis based on PI3K/AKT and MAPK signaling pathways

目的:基于磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(AKT)和丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)信号通路探讨防风桃红四物汤抗肝纤维化的作用机制。方法:利用BATMAN、TCMSP、Swiss Target Prediction等数据库检索药物作用靶点,及NCBI数据库检索疾病作用靶点,构建药物-疾病网络药理图;对疾病-药物共同靶点构建蛋白质-蛋白质相互作用网络并进行基因本体论(GO)、京都基因与基因组百科全书(KEGG)富集分析;将实验SD大鼠随机分为正常对照组、病理模型组、秋水仙碱组、防风桃红四物汤组、桃红四物汤组、防风水煎液组,每组10只;检测肝功能及肝纤维化指标变化;免疫印迹法与免疫组化检测相关细胞因子及相关通路蛋白表达情况。结果:防风桃红四物汤治疗肝纤维化的主要信号通路有PI3K/AKT和MAPK信号通路;药物治疗各组肝功能、肝纤维化标志物等异常指标的改善均优于对照组(P <0.05)。结论:防风可能主要通过PI3K/AKT和MAPK信号通路增效桃红四物汤抗肝纤维化的作用。

Objective:To explore the mechanism of the Fangfeng Taohong Siwu decoction(防风桃红四物汤)on anti-hepatic fibrosis based on PI3K/AKT and MAPK signaling pathways.Methods:We used BATMAN,TCMSP and Swiss Target Prediction databases to retrieve drug targets and NCBI databases to retrieve disease targets,then a pharmacological map of drug-disease network was constructed.We constructed PPI network for disease-drug co-targets and performed GO and KEGG enrichment analysis.We randomly divided the experimental SD rats into the normal control group,the pathological model group,the colchicine group,the Fangfeng Taohong Siwu decoction group,the Taohong Siwu decoction group and the Fangfeng decoction group,10 rats in each group.Liver function and liver fibrosis index changes were detected.Western Blot and immunohistochemistry were used to detect the expression of related cytokines and related pathway proteins.Results:The main signaling pathways PI3K/AKT and MAPK signaling pathways of hepatic fibrosis patient were treated with the Fangfeng Taohong Siwu decoction;the improvement of liver function,liver fibrosis markers and other abnormal indicators were better in the treatment groups than in the control group(P<0.05).Conclusion:Fangfeng(Radix Saposhnikoviae)may potentiate the anti-liver fibrosis effect of the Taohong Siwu decoction mainly through PI3K/AKT and MAPK signaling pathways.