基于网络药理学探讨化痰祛湿活血方治疗非酒精性脂肪性肝炎作用机制及实验验证

Mechanism and experimental verification of Huatan Qushi Huoxue recipe in the treatment of NASH based on network pharmacology

目的:基于网络药理学探讨化痰祛湿活血方治疗非酒精性脂肪性肝炎(NASH)的作用机制。方法:通过中药系统药理数据库与分析平台(TCMSP)获取化痰祛湿活血方的活性成分;从人体基因数据库(Genen Cards)中获得NASH治疗靶点,并与其潜在治疗靶点取交集获取关键基因;运用DAVID平台进行GO富集及KEGG通路分析,获取化痰祛湿活血方治疗NASH的生物功能和通路分析图。运用String数据库,建立PPI网络图;Cytoscape软件绘制复方-免疫机制图,复方-靶点-网络图;并采用动物实验验证部分靶点。结果:化痰祛湿活血方的靶点基因与NASH靶点基因的交集基因为372个;KEGG富集分析结果显示化痰祛湿活血方可能调控106条通路;GO富集分析得到MF 185个条目、BP 965个条目、CC 101个条目。大鼠实验验证化痰祛湿活血方可上调肝组织p-Akt蛋白表达,抑制p-NF-κB蛋白表达。结论:化痰祛湿活血方治疗NASH是多成分、多靶点、多通路相互作用的结果。经实验证实,其可能通过调控p-Akt和p-NF-κB的表达,从而参与炎症、免疫反应发挥效用。

Objective:To explore the mechanism of Huatan Qushi Huoxue decoction in treating NASH(non-alcoholic steatohepatitis) based on network pharmacology.Methods:The active components of Huatanqushi huoxue prescription were obtained by traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The therapeutic targets of NASH were obtained from the human gene database(Genen Cards),and the key genes were obtained by crossing with the potential therapeutic targets.GO Enrichment and KEGG pathway analysis were carried out by using the Davy Platform,and the bio function and pathway analysis of treating NASH with Huatan Qushi Huoxue prescription were obtained.The PPI network graph was established by using String database,the composite-immune mechanism graph,and the composite-target-network graph were drawn by Cytoscape software,and some targets were verified by animal experiments.Results:There were 372 cross genes between the target gene and NASH Target Gene of Hxf,and Kegg enrichment analysis showed that hxf might regulate 106 pathways.GO enrichment analysis resulted in 185 MF entries,965 BP entries,and 101 CC entries.The rat experiment proved that Huatanqushi huoxue recipe could up-regulate the expression of p-Akt protein and inhibit the expression of p-NF-κB protein.Conclusion:The treatment of NASH with Huatanqushi Huoxue decoction is the result of multi-component,multi-target and multi-channel interaction.The expression of p-AKT and p-NF-κB may play an important role in inflammation.