《伤寒论》方治疗糖尿病肾病的数据挖掘及核心药物的网络药理学研究

Data Mining of Treating Diabetes Nephropathic Disease with Formulas in Treatise on Cold Damage Diseases and Network Pharmacology Research on Core Drugs

目的:挖掘《伤寒论》方治疗糖尿病肾病的六经病证特点及方药应用规律,基于网络药理学分析核心药物的作用机制与靶点。方法:检索中英文数据库,收集《伤寒论》方治疗糖尿病肾病的研究,提取核心药物,用TCMSP、Genecards等数据库得到各药物有效成分靶点与疾病靶点,构建疾病-药物成分-靶点网络,并行GO和KEGG富集分析。结果:最终纳入文献17篇,方剂有大黄黄连泻心汤、五苓散、真武汤、抵当汤、葛根芩连汤、五苓散合四逆汤、小柴胡汤、小陷胸汤、芍药甘草汤、苓桂术甘汤、桂枝汤,桃核承气汤等。各方剂所治疗病证以太阳病最多,药物四气以寒性居多,应用频率在前20%的药物分别是甘草、桂枝、茯苓、白术。生物过程主要涉及肽的反应、平滑肌细胞增殖的调节等;细胞组分主要涉及膜侧面、溶解液泡等;分子功能主要涉及激素结合、核受体活性等;通路涉及肿瘤通路、腺苷酸激活蛋白激酶信号通路等。结论:《伤寒论》方治疗糖尿病肾病常从太阳病论治,核心药物是甘草、桂枝、茯苓、白术,PTPN1、CYP19A1可能为《伤寒论》方治疗糖尿病肾病的关键靶点。

application rules of formulas and drugs in the treatment of diabetes nephropathic disease(DND)with the formulas in Treatise on Cold Damage Diseases based on data mining,and analyze the mechanism of action and targets of core drugs based on network pharmacology.Methods:The Chinese and English databases were searched to collect the studies on the treatment of DND with the formulas in Treatise on Cold Damage Diseases.The core drugs were extracted,and the effective component targets and disease targets of each drug were obtained with TCMSP,Genecards and other databases.The disease-drug component-target,protein-protein interaction network was constructed,and GO and KEGG enrichment analyses were performed.Results:A total of 17 literature was ultimately included,involving the following formulas,such as Rhubarb and Coptis Heart-Draining Decoction,Five Substances Powder with Poria,True Warrior Decoction,Resistance Decoction,Pueraria and Scutellaria and Coptis Decoction,Five Substances Powder with Poria combined with Frigid Extremities Decoction,Minor Bupleurum Decoction,Minor Chest-Draining Decoction,Peony and Licorice Decoction,Poria and Cinnamon Twig and Atractylodes Macrocephala and Licorice Decoction,Cinnamon Twig Decoction,Semen Juglandis Purgative Decoction,etc.Greater yang syndrome disease was the most common type of disease treated by various drugs,and among the four natures of drugs,cold nature was the most common.The drugs with the highest frequency of application in the top 20%were as follows:Gancao(Radix Glycyrrhizae),Guizhi(Ramulus Cinnamomi),Fuling(Poria)and Baizhu(Rhizoma Atractylodis Macrocephalae).Biological processes mainly involved peptide reactions,regulation of smooth muscle cell proliferation,etc.The cell components mainly involved the side of the membrane,dissolved vacuoles,etc.Molecular functions mainly involved hormone binding,nuclear receptor activity,etc.Pathways involved tumor pathways,adenylate-activated protein kinase signaling pathways,etc.Conclusion:The formulas for treating DND in Treatise on Cold Damage Diseases mainly begin from greater yang diseases.Gancao(Radix Glycyrrhizae),Guizhi(Ramulus Cinnamomi),Fuling(Poria)and Baizhu(Rhizoma Atractylodis Macrocephalae).PTPN1 and CYP19A1 may be key targets for the treatment of DND.