摘要
目的采用UHPLC-Q-TOF-MS结合网络药理学探讨益肾清利活血方延缓慢性肾病大鼠肾纤维化的潜在作用机制。方法运用UHPLC-Q-TOF-MS对益肾清利活血方含药血清进行定性分析。采用SwissTargetPrediction、OMIM及GeneCards等数据库获取入血成分及疾病相关靶点,取交集后构建蛋白互作(PPI)网络,筛选关键靶点并进行GO功能和KEGG通路富集分析。采用Cytoscape软件构建“药物-入血成分-关键靶点-通路”网络,预测益肾清利活血方抗纤维化的作用靶点与信号通路,并构建肾纤维化模型对益肾清利活血方抗纤维化靶点和通路蛋白进行验证。结果共鉴定益肾清利活血方入血成分56个。化合物-疾病共有靶点97个,PPI网络分析筛选出关键靶点33个。KEGG富集与PPI网络分析发现,益肾清利活血方可能通过PI3K/Akt等通路发挥抗纤维化作用。动物实验结果表明,益肾清利活血方可降低纤维化大鼠的血肌酐(Scr)和尿素氮(BUN)水平,改善纤维化病变区域,抑制肿瘤坏死因子α(TNF-α)表达,降低PI3K/Akt通路蛋白表达。结论益肾清利活血方可能通过调控PI3K/Akt信号通路从而发挥抗纤维化作用。
OBJECTIVE To explore the potential mechanism of Yishenqinglihuoxue Formula(YSQLF)in treating chronic kidney disease fibrosis in rats based on UHPLC-Q-TOF-MS technology and network pharmacology.METHODS UHPLC-Q-TOF-MS was used for qualitative analysis of Yishenqinglihuoxue Formula-containing serum.Targets of the plasma constituents and the disease were retrieved from SwissTargetPrediction,OMIM,GeneCards,and other databases.Then the protein-protein interaction(PPI)network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment.Cytoscape software was employed to construct the"drug-compound-core target-pathway"network and the targets and signaling pathways of Yishenqinglihuoxue Formula against fibrosis were predicted.A model of renal fibrosis was established to verify the core targets and pathway proteins.RESULTS A total of 56 constituents migrating to blood of Yishenqinglihuoxue Formula were identified.97 common targets of the constituents and the disease and 33 core targets were screened out.KEGG enrichment and PPI network analysis showed that Yishenqinglihuoxue Formula may play a role in the treatment of fibrosis through PI3K/Akt and other pathways.Furthermore,the results of animal experiments showed that Yishenqinglihuoxue Formula could reduce the levels of Scr and BUN,improve fibrosis areas,inhibit the activation of the PI3K/Akt pathway,and reduce the protein expression of TNF-α.CONCLUSION Yishenqinglihuoxue Formula may play a role in the treatment of fibrosis by inhibiting PI3K/Akt signaling pathway and inhibiting TNF-αexpression.
作者
谢金丽
程萌
王一清
赵静
孙伟
陶静
XIE Jinli;CHENG Meng;WANG Yiqing;ZHAO Jing;SUN Wei;TAO Jing(The First Clinical Medical College,Nanjing University of Chinese Medicine,Nanjing 210023,China;Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China)
出处
《南京中医药大学学报》
CAS
CSCD
北大核心
2024年第11期1211-1222,共12页
Journal of Nanjing University of Traditional Chinese Medicine
基金
国家自然科学基金面上项目(82174295)。
