摘要
目的 探讨吕仁和教授治疗2型糖尿病的用药规律及其核心药物组成的作用机制.方法 收集吕教授2012年1月至2021年6月治疗2型糖尿病的病例,应用古今医案云平台对处方进行数据挖掘,获得核心药物组成.运用TCMSP获取核心药物化学成分及潜在靶点,通过GeneCards、OMIM、TTD、DrugBank等收集2型糖尿病的主要靶点,分别利用String、Metascape平台构建PPI网络,进行富集分析,使用Cytoscape3.8.0构建网络.结果 纳入的104首处方,共涉及中药203味,药性以微寒、平、温为主;药味以苦、甘、辛为主;归经以肝、脾经为主;药物功效以活血祛瘀药最多.关联规则分析共得到药物组合19种,核心药物组合为:丹参、川芎、赤芍、牡丹皮、太子参、葛根、当归.网络药理学分析核心药组活性成分66种,重复成分3种,药物靶点177个,药物-疾病交集靶点112个.核心药物调控2型糖尿病主要成分为丹参酮ⅡA、鼠尾草酚酮、β-谷甾醇、黄芩苷、刺芒柄花素等,关键靶点为PTGS2、ADRB2、PTGS1、SCN5A、RXRA、NCOA1,关键生物学进程和通路包括癌症信号通路、LDL信号通路、化学致癌作用通路、胰岛素抵抗信号通路等.结论 吕教授治疗2型糖尿病以补虚清热、通脉活血为主,其核心药物组合"丹参、川芎、赤芍、牡丹皮、太子参、葛根、当归"通过PTGS2、ADRB2、PTGS1、SCN5A、RXRA、NCOA1等蛋白基因的表达,介导癌症信号通路、LDL信号通路、化学致癌作用通路、胰岛素抵抗信号通路,达到治疗2型糖尿病的作用.
Abstract
Objective This study aims to investigate the medication patterns employed by Professor Lyu Renhe for treating type 2 diabetes mellitus and unravel the mechanism underlying the main pharmacological components.Methods Clinical cases of Professor Lv's treatment for type 2 diabetes mellitus from January 2012 to June 2021 were collected.Data mining was conducted using the Ancient and Modem Medical Case Cloud Platform to extract the core drug composition from the prescriptions.TCMSP was utilized to obtain the chemical composition of the core drugs and their potential targets.Major targets for type 2 diabetes were collected from GeneCards,OMIM,TTD,DrugBank,and other sources.Protein-Protein Interaction(PPI)networks were constructed using String and Metascape platforms,followed by enrichment analysis.The network was visualized using Cytoscape 3.8.0.Results A total of 104 prescriptions were included in the analysis,containing 203 herbal ingredients.These herbs were primarily categorized as slightly cold,flat,or warm in nature,with bitter,sweet,and pungent tastes.The liver and spleen meridians were most commonly targeted.The drugs with efficacy in promoting blood circulation and eliminating blood stasis were predominant.Association rule analysis identified 19 drug combinations.The core drug combinations include Danshen(Radix et Rhizoma Salviae Miltiorrhizae),Chuanxiong(Rhizoma Chuanxiong),Chishao(Radix Paeoniae Rubra),Mudanpi(Cortex Moutan),Taizishen(Radix Pseudostellariae),Gegen(Radix Puerariae Lobatae),and Danggui(Radix Angelicae Sinensis).Network pharmacological study of the core combinations revealed 66 active ingredients,3 duplicate ingredients,177 drug targets,and 112 drug-disease intersection targets.The primary constituents of the core medications used for managing type 2 diabetes include tanshinone ⅡA,rhamnolone,β-sitosterol,baicalin,and spiny mangosteen,among others.The primary targets comprised PTGS2,ADRB2,PTGS1,SCN5A,RXRA,and NCOA1.A number of biological processes and pathways are involved in treating type 2 diabetes,including cancer signaling,LDL signaling,chemical oncogenic action,and insulin resistance signaling.Conclusion Professor Lyu treats type 2 diabetes primarily by tonifying deficiency,clearing heat,promoting blood,and dredging meridians.The core combination of herbal medicines,including Danshen,Chuanxiong,Chishao,Mudanpi,Taizishen,Gegen,and Danggui,regulates the expression of protein genes such as PTGS2,ADRB2,PTGS1,SCN5A,RXRA,and NCOA1.These genes mediate cancer signaling pathways,LDL signaling pathways,carcinogenic pathways,and insulin resistance signaling pathways,thereby achieving therapeutic effects in the treatment of type 2 diabetes.
基金项目
国家重点研发计划(2018YFC1704100)
北京中医药大学东直门医院科技创新专项(DZMKJCX-2020-008)
维普
万方数据