目的 探讨通络地龟汤治疗糖尿病肾病（DKD）的潜在作用机制。方法 GeneCards、DisGeNET、OMIM、Drug Bank数据库收集DKD疾病靶点，TCMSP和BATMAN-TCM数据库分析得到通络地龟汤的有效活性成分及其对应的靶点；STRING数据库构建PPI网络图；Cytoscape软件建立通络地龟汤有效活性成分与DKD关键作用靶点网络图；DAVID数据库对靶点进行GO和KEGG通路富集分析；GEO芯片数据库对上述关键靶点进行验证；使用STZ腹腔注射复制1型糖尿病小鼠模型并采用通络地龟汤干预，Western Blot以及qPCR进行验证。结果 通过数据库进行有效筛选得到128个药物活性成分，共涉及720个作用靶点，得到通络地龟汤与DKD共同靶点588个，共同靶点主要相关的生物学过程有2817种，分子功能有312种，细胞组分有132种，作用在184条信号通路上发挥治疗DKD的作用，其中关键通路为MAPK信号通路。通过GEO数据库下载差异基因数据进行验证，证实ALB和VEGFA为通络地龟汤发挥治疗作用的关键基因，动物实验表明通络地龟汤能够促进ALB和VEGFA的表达，减轻DKD肾损伤。结论 本研究发现通络地龟汤可能通过多靶点、多功能、多通路治疗DKD，ALB和VEGFA可能为其中的关键靶点，MAPK通路为其发挥治疗作用的关键通路。

Objective To explore the potential mechanism of Tongluodigui Decoction in the treatment of Diabetic kidney disease(DKD).Methods Collect DKD disease targets through GeneCards, DisGeNET, OMIM, Drug Bank databases, and analyze the effective active ingredients of Tongluodigui Decoction and their Acorresponding targets through TCMSP and BATMAN-TCM database analysis; STRING database to build a PPI network diagram. Cytoscape software to build a network diagram of the effective active ingredients of Tongluodigui Decoction and DKD key targets. DAVID database to conduct GO and KEGG pathway enrichment analysis on the targets. GEO The chip database verifies the above-mentioned key targets; uses STZ intraperitoneal injection to replicate type 1 diabetes mouse models and Western Blot and qPCR for verification.Results Effectively screened through the database, 128 active ingredients were obtained, involving 720 targets, and 588 common targets of Tongluodigui Decoction and DKD were obtained. There are 2817 biological processes related to common targets. There are 312 kinds of functions and 132 kinds of cell components, which act on 184 signal pathways to treat DKD, among which the key pathway may be the MAPK signal pathway. Verification by downloading differential gene data from GEO database confirms that ALB and VEGFA are the key genes for Tongluodigui Decoction to play a therapeutic role. Animal experiments show that Tongluodigui Decoction can promote the expression of ALB and VEGFA and reduce DKD kidney damage.Conclusion This study found that Tongluodigui Decoction may treat DKD through multiple targets, multiple functions, and multiple pathways. ALB and VEGFA may be the key targets, and the MAPK pathway is the key pathway for its therapeutic effect.

R2-03

河南省自然科学(202300410256)；河南省重点研发与推广专项(科技攻关)项目(202102310505)；国家中医临床研究基地科研项目(2019JDZX2119)