基于网络药理学探讨金匮肾气丸治疗糖尿病肾病的作用机制  

Exploration of Mechanisms of Jinkui Shenqi Pill in Treatment of Diabetic Nephropathy Based on Network Pharmacology

作　　者：王晓芳 陈玮 黄国顺 周恩超[1] WANG Xiaofang;CHEN Wei;HUANG Guoshun;ZHOU Enchao(Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,Jiangsu,China)

机构地区：[1]南京中医药大学附属医院,江苏南京210029

出　　处：《实用中医内科杂志》2021年第12期24-27,I0011-I0015,共9页Journal of Practical Traditional Chinese Internal Medicine

基　　金：国家自然科学基金(81873270);江苏省“六大人才高峰”高层次人才项目(WSN-012);江苏省中医院“高峰学术”人才项目(y2018rc17)。

摘　　要：目的应用网络药理学及分子对接等手段探讨金匮肾气丸治疗糖尿病肾病的可能作用机制。方法通过TCMSP(Traditional Chinese Medicine System Pharmacology Database and Analysis Platform)收集金匮肾气丸有效成分及作用靶点;GeneCards、OMIM、PharmGkb、TTD和DrugBank等数据库查询糖尿病肾病相关靶点,筛选药物和疾病的交集靶,提取核心网络,并对核心靶点进行GO和KEGG富集分析,最终主要有效成分与核心靶点进行分子对接,得到可能结合模型。结果金匮肾气丸有效成分48个,核心化合物为:槲皮素、山柰酚、薯蓣皂苷元等,对应靶点194个,糖尿病肾病疾病靶点3054个,二者共有靶点128个,提取核心基因11个,分别为MYC、MAPK8、JUN、TNF、RELA、ESR1、MAPK1、AKT1、NR3C1、TP53、FOS。GO富集分析提示主要涉及氧化应激、细胞化学应激反应、药物反应等通路,KEGG(Kyoto Encyclopedia of Genes and Genomes)则主要涉及流体剪切应力与动脉粥样硬化信号通路、人巨细胞病毒感染、糖尿病并发症中的AGE-RAGE信号通路等。提取核心靶点网络后,分别将TNF(tumor necrosis factor)、TP53(Tumor Protein P53)及AKT1(Protein Kinase B)与有效成分山奈酚、薯蓣皂苷元、槲皮素进行分子对接。结论该研究系统揭示了金匮肾气丸治疗糖尿病肾病的作用机制,其疗效发挥与氧化应激、微炎症状态、肾纤维化等相关。Objective To explore the possible mechanism of Jinkui Shenqi Pill in the treatment of diabetic nephropathy by means of network pharmacology and molecular docking. Methods The effective compounds and the corresponding target proteins of Jinkui Shenqi Pill were determined and screened by using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP) database. And diabetic nephropathy genes were obtained from the GeneCards Database, OMIM Database, PharmGkb, TTD and DrugBank. The core target network was extracted, and the core targets were enriched by GO and KEGG. Finally, the main effective components were docked with the core targets, and the possible binding model was obtained. Results There were 48 effective components in Jingui Shenqi Pill, with 194 corresponding targets and the core compounds were quercetin, kaempferol, diosgenin, etc. And there were 3054 targets for diabetic nephropathy. Between Jinkui Shenqi Pill and diabetic nephropathy, there were 128 common targets. The core genes were extracted and the results were as follows: MYC,MAPK8,JUN,TNF,RELA,ESR1,MAPK1,AKT1,NR3 C1,TP53 and FOS. GO enrichment analysis was mainly involved in oxidative stress, cytochemical stress and drug response, while KEGG(Kyoto Encyclopedia of Genes and Genomes) AGE-RAGE was involved in fluid shear stress and atherosclerosis signal pathway, human cytomegalovirus infection, diabetic complications and so on. After the core target network was extracted, TNF(tumor necrosis factor),TP53(Tumor Protein p53) and AKT1(Protein Kinase B) were respectively docked with kaempferol, diosgenin and quercetin. Conclusion The study systematically reveals the mechanism of Jinkui Shenqi Pill to treat diabetic nephropathy, and its curative effect is related to oxidative stress, micro-inflammatory state, renal fibrosis and so on.

关 键 词：网络药理学 金匮肾气丸 糖尿病肾病 

分 类 号：R255.4[医药卫生—中医内科学]