基于网络药理学探讨血府逐瘀汤治疗甲状腺功能减退症的作用机制

Discussion on the Mechanism of Xuefu Zhuyu Decoction in Treating Hypothyroidism Based on Network Pharmacology

目的:基于网络药理学探讨血府逐瘀汤治疗甲状腺功能减退症的作用机制。方法:运用中医药系统药理学数据库与分析平台(TCMSP)、本草组鉴(HERB)平台筛选出血府逐瘀汤组成药物的活性成分,利用有机小分子生物活性数据库(PubChem)查找活性成分的化学结构,根据化学结构在SwissTargetPrediction数据库预测活性成分的潜在靶点。在Genecards数据库及Disgenet数据库中检索甲状腺功能减退症的相关靶点。利用韦恩图获得药物靶点及疾病靶点的交集靶点基因。利用STRING数据库对药物与疾病交集靶点进行蛋白质相互作用网络构建,获得血府逐瘀汤治疗甲状腺功能减退症的关键靶点。利用David数据库对交集靶点进行基因组百科全书(KEGG)信号通路与基因本体论(GO)功能富集分析。结果:得到药物有效成分208个,药物靶点1066个,甲状腺功能减退症靶点1386个,最终取交集靶点195个,KEGG信号通路20条。血府逐瘀汤治疗甲状腺功能减退症的关键靶点为STAT3、EP300、AKT1、MAPK1。关键的信号通路包括:肿瘤信号通路、糖尿病并发症中的AGE-RAGE信号通路等。结论:本研究初步揭示了血府逐瘀汤多成分、多靶点、多途径治疗甲状腺功能减退症的机制,为血府逐瘀汤的临床开发利用提供了依据。

Objective: To explore the mechanism of Xuefu Zhuyu decoction in treating hypothyroidism based on network pharmacology. Methods: The active components of Xuefu Zhuyu Decoction were screened by TCM Pharmacology Database and Analysis Platform (TCMSP) and HERB Platform, and the chem-ical structure of the active components was found by PubChem, and the potential targets of the ac-tive components were predicted in SwissTargetPrediction database according to the chemical structure. Searching the related targets of hypothyroidism in Genecards database and Disgenet da-tabase, the intersection target genes of drug targets and disease targets were obtained by Wayne diagram. Protein interaction network was constructed for the intersection targets of drugs and dis-eases by using STRING database, and the key targets of Xuefuzhuyu decoction in treating hypothy-roidism were obtained. Using David database, the signal pathway of KEGG and the function enrich-ment of GO were analyzed. Results: 208 active ingredients, 1066 drug targets and 1386 hypothy-roidism targets were obtained. Finally, 195 intersecting targets and 20 KEGG signal pathways were selected. The key targets of Xuefu Zhuyu decoction in treating hypothyroidism are STAT3, EP300, AKT1 and MAPK1. Key signal pathways include: tumor signal pathway, AGE-RAGE signal pathway in diabetic complications, etc. Conclusion: This study initially revealed the mechanism of Xuefu Zhuyu Decoction in treating hypothyroidism with multi-components, multi-targets and multi-channels, which provided a basis for the clinical development and utilization of Xuefu Zhuyu Decoction.