基于“异病同治”探究经典名方真武汤治疗心肾交集性疾病的网络药理学分子机制

Study on Molecular Mechanism of Zhenwu Decoction for“Different Diseases with Same Treatment”in Treating Intersection Disease of Heart and Kidney Based on Network Pharmacology

目的基于异病同治理论探究经典名方真武汤治疗心肾交集性疾病的网络药理学分子机制。方法综合利用中药整合药理学计算平台(TCM-IP)的中药材数据库、中药成分数据库和疾病靶标数据库的数据信息和分析功能,对真武汤治疗慢性心衰和糖尿病肾病的作用靶标、信号通路进行预测,分析二者的作用靶点、信号通路之间的关联性,探究该方"异病同治"治疗心肾交集性疾病的分子机制。结果对真武汤预测共得到280个活性成分,包括生物碱、皂苷、内酯、有机酸等成分;筛选出治疗慢性心衰115个核心靶标,治疗糖尿病肾病175个核心靶标,其中共同靶标包括谷氨酸脱羧酶2(GAD2)、葡萄糖激酶(GCK)、谷氨酰-脯氨酰-tRNA合成酶(EPRS)、细胞色素C氧化酶5A抗体(COX5A)、AMPA离子能谷氨酸受体2(GRIA2)等;涉及谷氨酸能突触、神经系统、精氨酸和脯氨酸代谢、苯丙胺成瘾以及血管内皮生长因子信号通路、酪氨酸激酶受体信号通路、促性腺激素释放激素信号通路等相关生物过程和信号通路。结论推测真武汤通过调节中枢神经"下丘脑-垂体"系统、内分泌和血液循环系统维持全身体液平衡,保持内环境稳定,并介导能量代谢和炎症反应过程达到治疗心肾交集性疾病目的,为进一步深入研究其作用机理提供了科学依据。

Objective The network pharmacology and molecular mechanism of treating heart and kidney intersects diseases with Zhenwu Decoction are explored based on the theory of treating different diseases with the same treatment.Methods By comprehensively using the data information and analysis function of TCM integrated pharmacology computing platform(TCM-IP)database of Chinese medicinal materials,TCM composition database and disease target database,the target and signal pathway of Zhenwu Decoction in the treatment of chronic heart failure and diabetic nephropathy were predicted,and the correlation between the target and signal pathway of Zhenwu Decoction was analyzed,so as to explore the molecular mechanism of this recipe"treating different diseases with the same treatment"in the treatment of heartkidney intersection disease.Results A total of 280 active ingredients,including alkaloids,saponins,lactones and organic acids,were predicted for Zhenwu Decoction.115 core targets selected for the treatment of chronic heart failure,175 core targets for the treatment of diabetic nephropathy.Among them,common targets include glutamate decarboxylase 2(GAD2),glucokinase(GCK),glutamylproline tRNA synthase(EPRS),cytochrome C oxidase 5A antibody(COX5A),AMPA ionosergic glutamate receptor 2(GRIA2),etc.;It involves glutamate synapses,nervous system,arginine and proline metabolism,phenylalanine addiction,vascular endothelial growth factor signaling pathway,tyrosine kinase receptor signaling pathway,gonadotropin releasing hormone signaling pathway and other related biological processes and signaling pathways.Conclusion This study speculated that that Zhenwu Decoction could achieve the purpose of treating heart and kidney diseases by regulating the central nervous system"hypothalamic-pituitary"system,endocrine system and blood circulation system,maintaining the balance of body fluids,maintaining the stability of internal environment,and mediating the process of energy metabolism and inflammatory reaction,thus providing scientific basis for further research on its mechanism of action.