中医药治疗糖尿病肾脏疾病湿热血瘀证用药规律及作用机制

Medication Rule and Action Mechanism of TCM in Treatment of Diabetic Kidney Disease(Dampness Heat and Blood Stasis Syndrome)

目的:基于真实世界诊疗数据,挖掘中医药治疗糖尿病肾脏疾病湿热血瘀证用药规律,并分析核心药物可能的作用机制。方法:通过频次分析、聚类分析、因子分析、复杂网络分析等统计学方法对来源于3所医院的489例湿热血瘀型糖尿病肾脏疾病患者的临床数据进行回顾性分析,挖掘中医药辨治糖尿病肾脏疾病湿热血瘀证的用药规律,并通过网络药理学及分子对接技术探讨核心药物发挥药效的潜在分子机制。结果:处方涉及325味中药,常用药物(频次≥30次)主要包括陈皮、黄连、茯苓、半夏、黄芪等,药物五味以苦、寒为主,归经以肝、脾经为主,系统聚类可聚为6类,复杂网络、关联规则等分析发现“黄连-赤芍-陈皮-竹茹”中药组合置信度最高。网络药理学研究筛选出“黄连-赤芍-陈皮-竹茹”活性成分40个,获得交集靶点140个,富集分析显示“黄连-赤芍-陈皮-竹茹”可能通过对无机物反应、细胞迁移及运动正调控、细胞因子受体结合、蛋白酶及激酶结合等生物学过程,作用于FOS、IFNG、TGF-β1、NFKB1A、MAPK8和IL-2等核心靶点的表达,进一步调控癌症的通路、糖尿病并发症中的晚期糖基化终产物-晚期糖基化终产物受体信号通路、低氧诱导因子-1信号通路、磷脂肌醇3-激酶-蛋白激酶B信号通路等,从而发挥治疗糖尿病肾脏疾病的作用。分子对接结果显示,主要活性成分与核心靶基因结合活性良好。结论:中医药治疗湿热血瘀型糖尿病肾脏疾病以清利湿热为主,“黄连-赤芍-陈皮-竹茹”可以多成分、多靶点、多通路、多机制治疗糖尿病肾脏疾病。

Objective:To explore the medication rules of traditional Chinese medicine(TCM)in the treatment of diabetic kidney disease(Damp Heat and blood stasis syndrome)based on real-world diagnosis and treatment data,and to analyze the possible mechanism of action of core drugs.Methods:A retrospective study was conducted on the clinical data of 489 patients with Damp Heat and blood stasis diabetic kidney disease from 3 hospitals with frequency analysis,cluster analysis,factor analysis,complex network analysis and other statistical methods,and the potential molecular mechanism of the core drugs was explored through network pharmacology and molecular docking technology.Results:The prescription involved 325 kinds of traditional Chinese medicines,and the commonly used drugs(frequency≥30 times)mainly included Chenpi(tangerine peel),Huanglian(coptis chinensis),Fuling(poria cocos),Banxia(pinellia ternata),Huangqi(astragalus),etc.The five flavors of the drugs were mainly bitter and cold,and the meridian tropism were mainly Liver and Spleen meridians.The systematic clustering could be clustered into 6 categories.Network pharmacology studies screened out 40 active ingredients of"Huanglian(coptis chinensis)-Chishao(radix paeoniae rubra)-Chenpi(tangerine peel)-Zhuru(caulis bambusae in taeniam)",and 140 intersecting targets were obtained.With enrichment analysis it was suggested that"Huanglian(coptis chinensis)-Chishao(radix paeoniae rubra)-Chenpi(tangerine peel)-Zhuru(caulis bambusae in taeniam)"may act on the expression of core targets such as FOS,IFNG,TGFB1,NFKB1A,MAPK8 and IL-2 through biological processes such as inorganic response,positive regulation of cell migration and motility,cytokine receptor binding,protease and kinase binding,etc.,to further regulate the pathway of cancer.The advanced glycation end products-advanced glycation end products receptor signaling pathway,hypoxia-inducible factor-1 signaling pathway,phospholipinositide 3-kinase-protein kinase B signaling pathway,etc.play a role in the treatment of diabetic kidney disease.The molecular docking results indicated that the main active ingredients had good binding activity to the core target genes.Conclusion:Traditional Chinese medicine(TCM)is mainly used to treat diabetic kidney disease with Damp Heat and blood stasis syndrome,and"Huanglian(coptis chinensis)-Chishao(radix paeoniae rubra)-Chenpi(tangerine peel)-Zhuru(caulis bambusae in taeniam)"can treat diabetic kidney disease with multiple components,multiple targets,multiple pathways and multiple mechanisms.