目的 通过网络药理学分析及实验验证初步探讨复方贞术调脂胶囊（Fufang Zhenzhu Tiaozhi Capsule， FTZ）干预糖尿病肾病（Diabetic Kidney Disease， DKD）的作用机制。方法 首先采用中药系统药理数据库和分析平台（TCMSP）、GeneCards、Comparative Toxicogenomics Database、STRING 11.0和DAVID 6.8数据库，综合分析FTZ在DKD中的潜在作用靶点；其次采用链脲佐菌素合并高脂饮食诱导的DKD模型小鼠为载体，通过检测空腹血糖、尿蛋白、肌酐、肾脏病理及潜在靶点的蛋白表达，初步验证FTZ改善DKD的作用机制。结果 生物信息学初步筛选出FTZ干预DKD的潜在靶点为STAT3、PI3K及AKT等。动物实验进一步发现FTZ能有效降低DKD小鼠空腹血糖（P<0.05）、尿蛋白（P<0.01）、肌酐（P<0.01），缓解肾脏病理损伤，下调肾脏组织中PI3K、p-AKT和STAT3的表达（P<0.05）。结论 FTZ改善DKD的机制可能与抑制PI3K/AKT及STAT3信号通路相关。本研究初步探讨了FTZ干预DKD的作用机制，为其临床防治DKD提供了实验基础和科学依据。

Objective To explore the mechanisms of Fufang Zhenzhu Tiaozhi Capsule (FTZ) in diabetic kidney disease (DKD) treatment through the network pharmacology analysis and animal validation.Method The TCMSP, GeneCards, CTD, STRING 11.0 and DAVID 6.8 databases were used for the biological information analysis of FTZ on DKD treatment. The DKD mice were established with streptozotocin (STZ) and high fat diet (HFD). Finally, fasting blood glucose (FBG), urinary protein, creatinine (SCr), renal pathomorphology and the target protein were detected by different biochemistry and molecular biology methods after the mice sacrificed.Result The potential targets of FTZ on DKD treatment were STAT3, PI3K and AKT, which were screened by bioinformatics. The animal experiment further showed that FTZ not only could effectively reduce FBG (P<0.05), urinary protein (P<0.01) and SCr (P<0.01), but also alleviate pathological damage of renal, and down-regulate the renal protein expression of PI3K, p-AKT and STAT3 in DKD mice (P<0.05).Conclusion The mechanisms of FTZ on DKD treatment may be related to the inhibition of PI3K/AKT and STAT3 signaling pathways. It provides an experimental basis and scientific evidence for the clinical prevention and treatment of DKD.

R285.5

广东省卫生健康委员会医学科学技术基金研究项目(B2020023):糖尿病肾病CD4 T细胞免疫代谢规律及病靶研究,负责人：杨祎琦;广州市科技局科技计划项目(202102020528):基于H3K4me3/TXNIP/ECM信号轴探讨复方贞术调脂胶囊治疗DKD的作用及机制研究,负责人：杨祎琦。