基于网络药理学探讨温肾宣痹方治疗膝骨关节炎的作用机制-东南大学学报医学版

基于网络药理学探讨温肾宣痹方治疗膝骨关节炎的作用机制

单位：1. 南京中医药大学附属医院/江苏省中医院骨伤科, 江苏南京 210029;
2. 南京中医药大学第一临床医学院, 江苏南京 210029

分类号：R681.8;R285

出版年·卷·期（页码）：2021·40·第六期（831-839）

摘要：

目的: 运用网络药理学的方法探讨温肾宣痹方治疗膝骨关节炎的作用机制。方法: 通过中药系统药理学分析平台(TCMSP)获得温肾宣痹方的相关活性成分以及靶点, 从GeneCards数据库、人类基因及遗传疾病在线目录(OMIM)数据库获取与膝骨关节炎相关的靶点, 两者的交集即为温肾宣痹方-膝骨关节炎疾病交集靶点; 筛选核心靶点基因, 使用蛋白互作与功能富集分析平台(STRING)构建靶点基因蛋白互作网络(PPI); 利用Cytoscape3.7.1软件构建温肾宣痹方-药物成分-交集靶点-疾病调控网络; 最后对交集靶点进行基因本体论(GO)富集分析及京都基因和基因组百科全书(KEGG)通路富集分析, 得出温肾宣痹方-膝骨性关节炎共同靶标的可能作用机制及相关信号通路。结果: 检索并筛选后共取得温肾宣痹方的196个有效成分和222个作用靶点, 通过GeneCards及OMIM数据库筛选出膝骨关节炎相关靶点基因2 064个, 取其交集得到药物-疾病交集靶基因116个, 筛选后得到核心靶点基因57个。GO富集结果显示, 分子功能主要聚集在细胞因子活性、细胞因子受体结合、核受体的活动、配体激活的转录因子活性、DNA结合转录激活因子活性等方面。KEGG富集分析显示, 作用机制可能与晚期糖基化终末产物及其受体(AGE-RAGE)协同信号通路、白介素-17(IL-17)信号通路、肿瘤坏死因子(TNF)信号通路等有关。结论: 温肾宣痹方治疗骨关节炎具有多系统、多靶点的特点, 其可能的机制是通过AGE-RAGE信号通路、IL-17信号通路、TNF信号通路作用于白介素-6(IL-6)、蛋白激酶B(AKT1)、血管内皮生长因子(VEGFA)等核心靶点, 干预炎症反应, 调节免疫功能, 抵抗氧化应激, 控制疾病的发生发展。

Objective: To find the new direction in preclinical study by explore the targets and signaling pathways of the effective ingredients of Whenshen Xuanbi Decoction in the treatment of knee osteoarthritis(KOA) through network pharmacology.Methods: Related active ingredients and potential targets were identified by using Traditional Chinese Medicine Systems Pharmacology(TCMSP), the disease targets corresponding to KOA were obtained by using GeneCards and OMIM database, standardizing all of the genes and then mapping the herbs-disease targets. The protein-protein interaction network was constructed on STRING online database, and then using the Cytoscape3.7.1 software to establish the TCM-Targets-Disease visual map as well as screen the core genes according to degree value. The gene ontology(GO) enrichment analysis and Kyoto Encyclopedia of genes and genomes(KEGG)enrichment analysis were carried out to display the related mechanisms and pathways of Wenshen Xuanbi Decoction in the treatment of KOA.Results: 196 active ingredients of Wenshen Xuanbi Decoction and 222 related targets were collected. By using the database of GeneCards and OMIM, 2 064 KOA related targets were collected, then 57 core targets were screened from 116 common targets of Wenshen Xuanbi Decoction-KOA. The analysis of GO enrichment showed that it was mainly related to cytokine activity, cytokine receptor binding, nuclear receptor activity, and ligand-activated transcription factor activity etc. The mechanism of action may be explained with interleukin-17(IL-17) signaling pathway, advanced glycation end products and its synergetic receptor(AGE-RAGE) signaling pathway in diabetic complications, tumor necrosis factor (TNF) signaling pathway.Conclusion: Wenshen Xuanbi Decoction has the characteristics of multi-component, multi-target and multi-system in treating KOA.Its mechanism of action may be through inhibiting the inflammatory response, regulating immune function, and resisting oxidative stress to control the occurrence and development of the disease by activating IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications and TNF signaling pathway.

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