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目的基于共表达蛋白相互作用网络探讨川芎嗪治疗冠心病的作用机制。方法根据数据库(STITCH与Chemprot)检索和药效团的虚拟筛选获得川芎嗪的靶点及靶点的蛋白相互作用信息,在Cytoscape中构建川芎嗪对应靶点的蛋白相互作用网络。结合基因表达谱分别构建疾病与正常2种状态下的共表达蛋白相互作用网络,运用基于边聚类系数的快速凝聚算法(FAG-EC)和Gene Ontology(GO)富集分析对疾病状态下的共表达网络进行模块聚类和功能注解,将获得的功能模块映射到正常状态下的共表达网络,得到相对应的功能模块,并对正常和疾病状态下的功能模块进行对比分析。结果川芎嗪主要通过调控免疫/炎症反应、细胞凋亡信号通路、血液循环、血红素代谢以及基础代谢等途径达到治疗冠心病的效果,而髓过氧化物酶(MPO)和血红素加氧酶-1(HMOX1)可能是冠心病治疗的关键靶点。结论从分子网络水平探讨了川芎嗪治疗冠心病的作用机制和关键靶点,为其临床应用提供了依据。
Objective To investigate the mechanism of ligustrazine in treating coronary heart disease (CHD) based on the co-expression protein interaction network. Methods According to the database (STITCH and Chemprot) search and virtual screening of pharmacophore, the protein interaction information of target and target of ligustrazine was obtained, and the protein interaction network of tetramethylpyrazine target site was constructed in Cytoscape. Combined with gene expression profiling, we constructed a co-expression protein interaction network between disease and normal condition. FAG-EC and Gene Ontology (GO) Co-expression network module clustering and functional annotation, the functional modules will be mapped to the normal state of the co-expression network, get the corresponding functional modules, and functional modules under normal and disease state comparative analysis. Results Tetramethylpyrazine can achieve the effect of treating coronary heart disease mainly by regulating immune / inflammatory reaction, apoptosis signal pathway, blood circulation, heme metabolism and basic metabolism, while the activity of myeloperoxidase (MPO) and heme oxygenase -1 (HMOX1) may be a key target for the treatment of coronary heart disease. Conclusion The molecular mechanism of tetramethylpyrazine in the treatment of coronary heart disease and its key targets were explored from the molecular network level, which provided a basis for its clinical application.