基于网络药理学和分子对接预测大黄素治疗脑缺血中风的作用机制

贾彩霞 陈建新 庞小涵 高阔 李京忠 张飞龙 王金平 王伟 徐晓新 赵慧辉

摘要 目的：利用网络药理学和分子对接的方法，预测大黄素治疗脑缺血中风的作用机制。方法：使用SymMap、TCMSP、OMIM、Drugbank数据库获得大黄素治疗脑缺血中风靶点，并通过Uniprot数据库进行格式统一及非人源靶点的去除。然后利用AlzData数据库进行大黄素治疗脑缺血中风的靶点在大脑细胞中的分布表达情况分析，使用DAVID数据库对其进行KEGG通路分析和GO分析，得到相关通路。结果：大黄素治疗脑缺血中风的潜在作用靶点共10个，分别为CASP3、KDR、PTGS1、TNF、MMP9、PRKCE、PTGS2、MYC、TP53，各自在大脑星形胶质细胞、小胶质细胞、内皮细胞等中有不同程度的表达，涉及KEGG相关富集通路12条、GO生物过程富集条目14条、GO细胞组分富集条目3条、GO细胞功能富集条目2条。分子对接结果发现与CASP3、KDR、PTGS1、TNF、MMP9结合较好。结论：大黄素可能主要通过CASP3、KDR、PTGS1、TNF、MMP9作用于细胞凋亡通路及炎症反应相关等通路来发挥治疗脑缺血中风的作用。

关键词 网络药理学;分子对接;脑缺血中风;大黄素;靶点;通路;机制

Mechanism Research of Emodin in the Treatment of Ischemic Stroke Based on Network Pharmacology and Molecular Docking

JIA Caixia1，CHEN Jianxin1，PANG Xiaohan1，GAO Kuo2，LI Jingzhong1，ZHANG Feilong1，WANG Jinping3，WANG Wei1，XU Xiaoxin1，ZHAO Huihui1

（1 Beijing University of Chinese Medicine，Beijing 100029，China; 2 Dongfang Hospital of Beijing University of Chinese Medicine，Beijing 100029，China; 3 China-Japan Friendship Hospital，Beijing 100029，China）

Abstract Objective：To research the mechanism of emodin in the treatment of ischemic stroke based on network pharmacology and molecular docking.Methods：Emodin targets for ischemic stroke were obtained by using SymMap，TCMSP，OMIM and Drugbank databases，and the format was unified and non-human targets were removed by Uniprot database.Then AlzData database was used to analyze the distribution and expression of emodin targets in brain cells for cerebral ischemia stroke.KEGG pathway and GO enrichment analysis was performed on the target of emodin for ischemic stroke using DAVID database to obtain the relevant pathway.Results：There were 10 potential targets for emodin in the treatment of ischemic stroke，which were CASP3，KDR，PTGS1，TNF，MMP9，PRKCE，PTGS2，MYC，TP53.They were expressed in astrocytes，microglia and endothelial cells in a different degrees.There were 12 KEGG related enrichment pathways，14 GO biological process enrichment items，3 GO cell component enrichment items，and 2 GO cell functional enrichment items related to ischemic stroke，and it had a good combination with CASP3，KDR，PTGS1，TNF and MMP9.Conclusion：Emodin may play a role in the treatment of ischemic stroke mainly through CASP3，KDR，PTGS1，TNF，MMP9 acting on apoptosis pathways and inflammation-related pathways.

Keywords Network pharmacology; Molecular docking; Ischemic stroke; Emodin; Target; Pathway; Mechanism

中圖分类号：R285文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.06.005

中风是世界范围内造成残疾甚至死亡很大比例的一种脑血管疾病[1]，分为缺血性中风和出血性中风，其中85%的中风是缺血性的[2]。缺血性脑中风是常见的脑血管病，是由脑血管狭窄或闭塞引起的，具有高并发率和高死亡率的特点[3]。在中医学中被认为是“中风”，李东垣曰：“中风为百病之长，乃气血闭而不行”[4]。因此，活血调气成为治疗中风的重要治则。《神农本草经》中记载大黄，性味苦寒，具有泻下通便、活血化瘀等功能，目前研究表明其含有的有效化合物有蒽醌类（如游离型蒽醌大黄素，结合型蒽醌大黄素甲醚葡萄糖苷）、多糖、鞣质等[5]。……