【摘要】 目的 研究天麻汤治疗缺血性脑卒中(cerebral ischemic stroke, CIS)的潜在靶点及作用通路以及天麻汤对小胶质细胞活性和Hub相关基因表达的影响，研究天麻汤治疗该疾病的作用机制。方法 在Disgenet、TTD、OMIM、Drugbank、KEGG数据库检索CIS的基因；利用TCMSP数据库和Uniprot数据库对天麻汤的药物化学成分进行检索和靶点预测；使用STRING网络平台构建PPI网络图；利用Cytoscape软件构建成分-靶点网络图；通过DAVID数据库筛选天麻汤治疗CIS的靶点基因并进行GO分析及KEGG通路分析；利用MTT检测天麻汤对小胶质细胞的活性；利用PCR实验检测Hub相关基因。结果 从天麻汤中共筛选出82个有效成分和729个疾病靶点。通过5大数据库获得缺血性脑卒中946个疾病相关靶点。通过Venny 2.1.0平台将天麻汤有效成分预测靶点与疾病靶点取交集，获得43个靶点基因。借助DAVID数据库进行KEGG富集分析发现天麻汤治疗CIS涉及NF-kB信号通路、TNF等信号通路。筛选出degree得分前10位关键基因是Bax、Bcl-2、PTGS2、caspase-3、IL6、TNF、AKT1、ESR1、IL-1β、SIRT1。天麻汤对正常的胶质细胞无毒性。与CIS组比较，CIS+1 g/mL天麻汤组Caspase-3和Bax降低(P<0.05),Bcl-2升高(P<0.05)。结论 天麻汤能抑制caspase-3和Bax的表达，促进Bcl-2的表达。更多还原

【Abstract】 Objective To investigate the potential targets and pathways of action of Tianma decoction in the treatment of ischemic stroke and the effect of Tianma decoction on the glial cells activity and Hub-related genes, expressin, and to explain the mechanism of action of Tianma decoction in the treatment of this disease.Methods The genes of ischemic stroke were searched in Disgenet, TTD, OMIM, Drugbank and KEGG databases. TCMSP database and Uniprot database were used to search and predict the drug chemical components of Tianma decoction. PPI network diagram was constructed by using STRING network platform. The component-target network diagram was constructed by using Cytoscape software. The target genes of Tianma decoction in the treatment of ischemic stroke were screened with DAVID database and analyzed with GO and KEGG pathway. MTT was used to detect the activity of Tianma decoction on glial cells. The HUB-related genes were detected by PCR.Results A total of 82 active components and 729 disease targets were screened from Tianma decoction. A total of 946 disease-related targets of ischemic stroke were obtained from 5 databases. Through Venny 2.1.0 platform, the prediction targets of active components of Tianma decoction were intersected with disease targets, and 43 target genes were obtained. KEGG enrichment analysis with DAVID database showed that Tianma decoction involved NF-kB signaling pathway and TNF signaling pathway in the treatment of ischemic stroke. The top 10 key genes in degree score were Bax, Bcl-2, PTGS2, caspase-3, IL6, TNF, AKT1, ESR1, IL-1β, and SIRT1. Experimental data showed that Tianma decoction was not toxic to normal glial cells. Compared with the CIS group, the CIS+1 g/mL Tianma decoction group showed decreased levels of caspase-3 and Bax(P<0.05), and increased level of Bcl-2(P<0.05).Conclusion Tianma decoction could inhibit the expression of cleaved caspase-3 and Bax, and promote the expression of Bcl-2.更多还原