基于网络药理学和实验验证分析补阳壮通饮治疗缺血性脑卒中的分子机制OA

Objective:To discover the mechanism of action of Buyang Zhuangtong Yin(BYZTY)in the treatment of isch-emic stroke(IS)by applying the principles of network pharmacology,molecular docking technology,and animal experiments.Methods:The potential active ingredients and their corresponding targets of 9 herbs,including Fufangteng,Huangqi,Daxueteng and others were screened by reviewing the relevant literatures and the TCMSP database,and then GeneCards,Drugbank,TTD,PharmGKB,and OMIM databases were utilized to find the related targets of IS.Afterwards,an online tool was used to draw a Venn diagram between the targets of BYZTY and the targets related to IS diseases to obtain the intersection targets,and these tar-gets were entered into the STRING database to obtain the protein-protein interaction network diagram.Then the data were import-ed into the Cytoscape 3.10.2 software,the CytoNCA plug-in was used to screen the key targets and draw the network relationship diagram of"drug-active ingredient-target".The target enrichment analysis was obtained from the DAVID database.In addition,by using AutoDock tools software,the key targets were molecularly docked with their corresponding active ingredients.Finally,in vi-vo experiments were conducted using rats to construct a middle cerebral artery occlusion model,which was taken after 2 weeks of drug treatment with BYZTY and its mechanism of action was verified and analyzed by using the Neurological deficit score,TTC staining,brain histopathological staining,Western blot,ELISA and other methods.Results:A total of 145 intersecting targets were obtained.Based on the Degree value,TNF,IL-6,and IL-1β were screened as the key targets.A total of 327 GO entries and 131 KEGG entries were obtained from the enrichment analyses.The binding activities between the key targets and their corre-sponding active ingredients were strong,and the binding was solid.The results of animal experiments showed that,compared to the model group,the BYZTY high-dose group had a more significant effect on reducing the score of neurological deficits.And it could effectively reduce the volume of infarction in brain tissue,the pathological damage in the ischemic penumbra,the content of inflammatory factors in plasma,and the expression of TNF-α,IL-6,and IL-1β proteins in brain tissue.Conclusion:BYZTY may be effective in treating IS by acting on the targets of TNF-α,IL-6,and IL-1β,thereby reducing the inflammatory response of the body.