摘要
目的采用网络药理学分析方法研究贝沙罗汀治疗脑缺血/再灌注损伤(cerebral ischemia reperfusion injury,CIRI)的作用机制。方法通过PharmMapper Server、GeneCards分别对贝沙罗汀和疾病的靶点进行预测,利用VE NNY 2.1.0得到贝沙罗汀作用于CIRI的靶点,并利用Cytoscape 3.8.2软件绘制PPI网络。利用R语言的cluster Profiler软件包对贝沙罗汀抗CIRI的潜在靶点进行GO富集分析和KEGG富集通路分析。结果找到贝沙罗汀相关靶点275个,脑缺血/再灌注损伤相关靶点513个,交集靶点73个,度值排名前10名的关键靶基因为ALB、AKT1、CASP3、JUN、MAPK1、MAPK8、MMP9、SRC、IGF1、ESR1。通过KEGG富集通路分析得到138条通路,结合相关文献,其中最为显著相关的有MAPK信号通路、细胞凋亡信号通路、PI3K-Akt信号通路、流体剪切应力与动脉粥样硬化信号通路等。结论贝沙罗汀通过多靶点、多途径治疗CIRI,其可能主要通过发挥抗凋亡、抗炎、抗氧化、抗凝等功能,起到抗CIRI的作用。
Objective To explore the mechanism of bexarotene in the treatment of cerebral ischemia reperfusion injury(CIRI)via network pharmacology.Methods PharmMapper Server was used to predict the targets of bexarotene,GeneCards was applied to retrieve the targets of the disease,and VENNY 2.1.0 was adopted to map the targets of bexarotene on CIRI.PPI networks of potential targets were constructed with software Cytoscape 3.8.2 before the R language package clusterProfiler was used for GO enrichment analysis and KEGG pathway analysis of the potential targets of bexarotene against CIRI.Results After mapping the predicted 275 targets of bexarotene with the 513 targets of cerebral ischemia/reperfusion injury,a total of 73 intersection targets were obtained.In the PPI network of potential targets,the top 10 key target genes were ALB,AKT1,CASP3,JUN,MAPK1,MAPK8,MMP9,SRC,IGF1 and ESR1.A total of 138 pathways were enriched by KEGG pathway analysis,among which the MAPK signaling pathway,apoptosis signaling pathway,PI3K-Akt signaling pathway,fluid shear stress and atherosclerosis signaling pathway were most significantly related to CIRI.Conclusion Bexarotene protects against CIRI possibly by acting on multiple targets and through multiple pathways,exerting anti-apoptotic,anti-inflammatory,anti-oxidant,anti-coagulative effects.
作者
石强
刘胜伟
沈正泽
陈昶
任忠洋
刘洁
胡毅
SHI Qiang;LIU Shengwei;SHEN Zhengze;CHEN Chang;REN Zhongyang;LIU Jie;HU Yi(The First People’s Hospital of Zigong Neurology Department,Zigong Sichuan 643000,China;Yongchuan Hospital of Chongqing Medical University department of pharmacy,Chongqing 402160,China;Jiangjin Hospital of Traditional Chinese Medicine,Surgery Department Chongqing 402284,China;Jiangjin Central Hospital of Chongqing,Department of Pharmacy Chongqing 402260,China)
出处
《中国药物警戒》
2022年第12期1332-1337,共6页
Chinese Journal of Pharmacovigilance
基金
国家自然科学基金资助项目(81701477)
重庆市自然科学基金科研项目(cstc2020jcyj-msxmX0434)
重庆医科大学附属永川医院资助项目(YJJC202009)。
关键词
贝沙罗汀
脑缺血再灌注
网络药理学
bexarotene
cerebral ischemia-reperfusion injury
network pharmacology
