基于网络药理学和实验验证探讨益气和血方治疗肝硬化的作用机制

Action mechanism of Yiqi Hexue Formula in the treatment of liver cirrhosis based on network pharmacology and experimental verification

目的:基于网络药理学和实验验证探讨益气和血方治疗肝硬化的作用机制。方法:首先从TCMSP及BATMAN-TCM数据库搜索益气和血方各中药的有效成分及其作用靶点,应用GeneCard、PharmGkb、OMIM、DrugBank、TTD数据库获得疾病靶基因。将药物潜在作用靶基因与疾病靶基因取交集,并绘制韦恩图,应用Cytoscape软件构建“活性成分-核心靶点”网络,利用R软件对交集基因进行KEGG通路分析。动物实验观察益气和血方对CCl4诱导的肝硬化模型大鼠组织病理学的影响,测定肝组织JAK2、STAT3 mRNA表达水平,对益气和血方治疗肝硬化的作用机制进行初步探讨。结果:通过数据库共筛选得到益气和血方治疗肝硬化的活性成分43个及靶点648个,KEGG通路分析显示益气和血方主要影响PI3K/Akt、MAPK、IL-17、JAK/STAT等信号通路。动物实验研究表明与模型组相比,益气和血方治疗组大鼠肝组织炎症与纤维化程度明显改善;益气和血方治疗组JAK2、STAT3 mRNA的表达明显下调,差异具有统计学意义(P<0.05)。结论:益气和血方能够通过多成分、多靶点、多条通路达到治疗肝硬化的目的,JAK2/STAT3信号通路参与肝硬化的形成,益气和血方能够改善肝硬化大鼠病理表现,其作用机制可能与抑制JAK2/STAT3信号通路传递有关。

Objective:To study the mechanism of Yiqi Hexue Formula in the treatment of liver cirrhosis based on network pharmacology and experimental verification.Methods:Firstly,the effective components and action targets of various traditional Chinese medicines in Yiqi Hexue Formula were searched from TCMSP and BATMAN-TCM databases.The disease target genes were obtained by using GeneCard,PharmGkb,OMIM,DrugBank and TTD databases.The potential target genes of drugs and disease target genes were intersected,and the Venn diagram was drawn.The"active ingredient-core target"network was constructed by Cytoscape software,and the KEGG pathway of the intersection genes was analyzed by R software.Animal experiments were conducted to observe the effect of Yiqi Hexue Formula on histopathology of CCl4-induced liver cirrhosis model rats,determine the expression levels of JAK2 and STAT3 mRNA in liver tissue,and preliminarily explore the mechanism of Yiqi Hexue Formula in the treatment of liver cirrhosis.Results:A total of 43 active components and 648 targets of Yiqi Hexue Formula for the treatment of liver cirrhosis were screened through the database.KEGG pathway analysis showed that Yiqi Hexue Formula mainly affected PI3K/Akt,MAPK,IL-17 and JAK/STAT signaling pathway.Animal experimental research showed that compared with the model group,the degree of inflammation and fibrosis in liver tissue of rats treated with Yiqi Hexue Formula was significantly improved;The expression of JAK2 and STAT3 mRNA decreased significantly in the treatment group of Yiqi Hexue Formula(P<0.05).Conclusion:Yiqi Hexue Formula can treat liver cirrhosis through multiple components,multiple targets and multiple pathways.JAK2/STAT3 signaling pathway is involved in the formation of liver cirrhosis.Yiqi Hexue Formula can improve the pathological manifestations of cirrhotic rats.Its mechanism may be related to inhibiting the transmission of JAK2/STAT3 signaling pathway.