基于网络药理学及分子对接探讨淫羊藿对顺铂诱导的肾损伤保护机制

Discussion on Epimedium Protective Mechanisms for Cisplatin-induced Renal Injury Based on Network Pharmacology and Molecular Docking

通过中药系统药理学数据库与分析平台TCMSP探索淫羊藿化学成分,在Gene Card中搜索肾损伤的相关基因,构建化学成分-作用靶点网络图、蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络图;借助DAVID进行通路富集分析(kyoto encyclopedia of genes and genomes,KEGG)和生物功能富集分析(biological function enrichment,GO),利用Schrodinger Maestro软件和在线工具进行分子对接验证,预测核心靶点;进行动物实验,取小鼠血清检测尿素氮(BUN)、肌酐(CRE)、肿瘤坏死因子α(TNF-α)、白介素6(IL-6)水平,苏木精-伊红(HE)染色观察肾脏病理结构变化。网络药理学共筛选出18个化合物与58个靶点蛋白参与网络构建,基因富集分析显示,涉及120个GO条目(P<0.05),KEGG信号通路共73条,分子对接表明,淫羊藿活性成分与关键靶点之间有较强的结合效果。动物实验表明,与模型组相比,淫羊藿水提物能使小鼠血清中BUN、CRE、IL-6、TNF-α水平降低;由HE染色结果得,细胞核形状由不规则变得完整,肾小管扩张,炎性细胞浸润情况都有所改善。本研究从整体上分析了其保护机制可能通过抑制炎症反应,减少细胞凋亡,为淫羊藿临床应用提供科学依据。

The chemical composition of Epimedium was explored through the pharmacology database and analysis platform of traditional Chinese medicine system(TCMSP),searched the related genes of kidney injury in GenenCard database,constructed the network map of chemical composition-action target and protein-protein interaction(PPI)network.KEGG and GO enrichment analysis were carried out with the help of DAVID,and molecular docking verification was carried out by using Schrodinger Maestro software and online tools to predict core targets.The serum levels of blood urea nitrogen(BUN),creatinine(CRE),tumor necrosis factor alpha(TNF-α)and interleukin 6(IL-6)were detected in the serum of mice,and the pathological changes of kidneys were observed by HE staining.A total of 18 compounds and 58 target proteins were screened for network construction in network pharmacology.Gene enrichment analysis showed that 120 GO entries(P<0.05)and 73 KEGG signaling pathways were involved.The results of molecular docking showed that the core target had strong binding energy with chemical components.Animal experiments showed that the water extract of Epimedium could reduce the serum BUN、CRE、IL-6、TNF-αlevel of mice compared with the model group.H&E staining showed that the nucleus shape changed from irregular to complete,renal tubular dilatation and inflammatory cell infiltration improved.This study analyzes its protective mechanism as a whole and may reduce apoptosis by inhibiting inflammatory response,providing scientific basis for the clinical application of Epimedium.