基于网络药理学及分子对接研究探索生姜泻心汤治疗化疗相关腹泻的作用机制  

Study on the mechanism of Shengjiang Xiexin decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacology and molecular docking

作　　者：高宇[1,2] 孙建荣 邓超 贾立群[2] GAO Yu;SUN Jian-rong;DENG Chao;JIA Li-qun(Beijing University of Chinese Medicine,Beijing 100029,China;China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]北京中医药大学,北京100029 [2]中日友好医院,北京100029

出　　处：《海南医学院学报》2022年第13期1010-1020,共11页Journal of Hainan Medical University

基　　金：国家自然科学基金项目青年科学基金项目(81904001);首都卫生发展科研专项(首发2018-1-4061);国家中医药管理局重大疑难疾病中西医临床协作能力建设项目(2019-ZX-005);中日友好医院院内课题(2019-1-QN-56)。

摘　　要：目的:应用网络药理学研究方法预测生姜泻心汤治疗化疗相关腹泻的作用靶点及其潜在的作用机制。方法:检索中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)筛选出生姜泻心汤的有效成分和作用靶点;化疗相关腹泻的疾病靶点检索基因名片数据库(Gene Cards)得到;使用R软件分析得到药物与疾病共同作用靶点;构建药物-有效成分-作用靶点-疾病的互作网络,探索关键有效成分及靶点;蛋白质互作网络由STRING平台构建,可以进行视觉可视化分析;使用R包进行GO和KEGG靶点功能通路富集分析。结果:筛选后共得出216个药物有效成分和276个相应靶点,并得到1 764个疾病相关作用靶点,其中有173个是药物与疾病的共同靶点。GO富集分析共得到2 427条生物过程,168项分子功能相关,79项细胞组成相关。KEGG通路富集得到169条KEGG信号通路。结论:生姜泻心汤治疗化疗相关腹泻可能是通过STAT3、AKT1、MAPK3、JUN、MAPK1、RELA、IL6等蛋白作用,发生DNA结合转录因子结合、细胞因子受体结合、脂多糖应答、化学应激反应等生物学过程,并主要富集在Toll样受体信号通路、肿瘤坏死因子(TNF)信号通路、乙型肝炎(hepatitise B)信号通路、A型流感病毒(inlfuenza A)等信号通路上,发挥抗炎和修复屏障等作用。Objective:To explore the key targets and mechanism of Shengjiang Xiexin decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacological methods.Methods:The effective components and corresponding target proteins of Shengjiang Xiexin decoction were screened by TCMSP,and the targets of chemotherapy-induced diarrhea were screened by the Gene Cards. R software was used to obtain the common targets of drugs and diseases,and the“component-targetdisease”network diagram was constructed by Cytoscape3.8.0 software. The string database was used to draw the protein interaction network,and the Bioconductor software was used to perform GO function and KEGG pathway enrichment analysis on effective targets. Results:The result showed that 216 components and 276 effective targets were screened. There were 1 764 chemotherapy-induced diarrhea targets. The 173 common targets were obtained through Venny diagram. The GO function analysis found2 427 items of biological process,168 items of molecular function and 79 items of cellular component. The KEGG pathway analysis found 169 items. Conclusion:The protein interaction network shows that STAT3,AKT1,MAPK3,JUN,MAPK1,RELA,IL6,etc. might be the key targets for Shengjiang Xiexin decoction in treatment of chemotherapy-induced diarrhea. GO biological processes include DNA-binding transcription factor activity,cytokine receptor binding,cytokine activity,response to lipopolysaccharide,cellular response to chemical stress. The KEGG pathways involve mainly in Toll-like receptor signaling pathway,TNF signaling pathway,inlfuenza A signaling pathway,hepatitis B signaling pathway and other pathways that play the role in anti-inflammatory and repairing barrier.

关 键 词：生姜泻心汤 化疗相关腹泻 网络药理学 作用机制 分子对接 

分 类 号：R285[医药卫生—中药学]