海南医科大学学报

目的:基于网络药理学方法筛选芪参汤的主要活性成分并预测其治疗非酒精性脂肪性肝病(NAFLD)的作用靶点,并通过实验验证。方法:通过数据库筛选芪参汤的主要活性成分和NAFLD的疾病靶点;采用Cytoscape软件和String数据库构建药物-疾病-靶点网络和PPI;采用DAVID数据库进行GO和KEGG富集分析;通过HE染色、油红染色、血清生化指标及Western blot法验证芪参汤对高脂饮食构建NAFLD小鼠模型的作用机制。结果:本研究一共筛选到芪参汤活性化合物207个,95个药物疾病靶点,KEGG富集分析结果显示芪参汤治疗NAFLD的机制涉及脂肪细胞因子、胰岛素信号途径、脂肪酸生物合成等。实验结果显示,芪参汤能够明显降低NAFLD大鼠肝脏NAS评分和油红O染色面积(P<0.05)。同时,芪参汤明显降低NAFLD大鼠血清葡萄糖、胰岛素、HOMA-IR、TC、TG、AST及ALT水平(P<0.05)。此外,芪参汤能够明显上调肝组织中p-INSRβ的表达,下调SREBP-1C、FAS和p-ACC的表达(P<0.05)。结论:芪参汤能够通过胰岛素信号通路改善NAFLD大鼠胰岛素抵抗,从而改善NAFLD脂肪沉积和肝损伤。除此之外,芪参汤还能够通过多途径、多靶点达到治疗NAFLD的作用。

Objective: To screen the main active components of Qishen decoction by network pharmacology and predict the target of its treatment for nonalcoholic fatty liver disease(NAFLD), and to verify it by experiments. Methods: The main active components of Qishen decoction and the disease target of NAFLD were screened through the database; the drug disease target network and PPI were constructed by the software of Cytoscape and string database; the enrichment of go and KEGG were analyzed by the database of DAVID; HE staining, red oil O staining, serum biochemical index and Western blot were used to verify the effect mechanism of Qishen decoction on NAFLD. Results: A total of 207 active compounds and 95 drug-disease-targets of Qishen Decoction were selected in this study. The results of KEGG enrichment analysis showed that the mechanism of Qishen decoction in the treatment of NAFLD involved adipocytokines, insulin signaling pathway, fatty acid biosynthesis, etc. The results showed that Qishen decoction could significantly reduce the liver NAS score and oil red O staining area of NAFLD rats(P<0.05). Meanwhile, Qishen decoction significantly reduced the levels of serum glucose, insulin, HOMA-IR, TC, TG, AST and ALT in NAFLD rats(P<0.05). In addition, Qishen decoction can significantly upregulate the expression of p-INSR β in liver tissue, downregulate the expression of SREBP-1 c, Fas and p-ACC(P<0.05). Conclusion: Qishen decoction can improve the insulin resistance of NAFLD rats through insulin signaling pathway, so as to improve NAFLD fat deposition and liver injury. In addition, Qishen decoction can also achieve the therapeutic effect of NAFLD through multiple channels and targets.