目的 整合Meta分析和网络药理学策略，评价补肾活血汤治疗糖尿病肾病的临床疗效，初步探索其干预机制。方法 首先通过Meta分析，全面检索补肾活血汤治疗糖尿病肾病随机对照试验（randomized controlled trial，RCT）研究的中英文文献，基于纳排标准，确定定量文献，采用Review Manager对纳入数据统计分析；然后基于网络药理学，筛选补肾活血汤中的化学成分及其作用靶点、疾病靶点、共有靶点等相关信息，随后基于生物信息学技术，进行关键通路的相关注释，探讨补肾活血汤干预糖尿病肾病的潜在机制。结果 共纳入19篇RCTs文献，共计1502例受试者，Meta分析结果显示，在有效率、血糖、血脂以及肾功能指标方面，治疗组优于对照组，具有统计学差异（P<0.05）；通过在线数据库共得到559个化学成分和2306个潜在靶标，其中201个成分、145个靶标和185条通路与干预的糖尿病肾病关系极为密切，主要涉及晚期糖基化终末产物/AGEs受体（advanced glycation end products/AGEs receptor，AGE-RAGE）信号通路、胰岛素抵抗、肿瘤坏死因子（tumor necrosis factor，TNF）信号通路、丝裂原活化蛋白激酶（mitogen activated protein kinase，MAPK）信号通路等分子过程。结论 现有证据表明，在西医常规治疗基础上加用补肾活血汤能提高糖尿病肾病的临床疗效，并在降糖、调血脂和保护肾功能方面具有一定优势，但整体证据级别较低，仍需进行大规模、多中心的RCTs进一步支持；补肾活血汤干预糖尿病肾病是多成分、多靶标共同作用的综合性结果，其主要通过干预氧化应激、炎症反应、多元醇通路、胰岛素途径、糖脂代谢、细胞凋亡等途径达到治疗糖尿病肾病的目的。在Meta分析和网络药理学联合应用的基础上进行了科研尝试，也为其他药物的临床评价及机制研究提供参考。

Objective Meta analysis and network pharmacology were integrated to evaluate the clinical effect of Bushen Huoxue Decoction (补肾活血汤) in the treatment of diabetic nephropathy. Methods First of all, through Meta analysis, the Chinese and English literature on the treatment of diabetic nephropathy RCTs by Bushen Huoxue Decoction was searched comprehensively. Based on the criteria of inclusion and exclusion, the quantitative literature was determined, and the statistical analysis of the included data was carried out by Review Manager. Secondly, based on the network pharmacology, the chemical components were screened out, the target of action, the target of disease, the common target and other related information in Bushen Huoxue Decoction. Then, based on the bioinformatics technology, the key pathway was annotated, and the potential mechanism of Bushen Huoxue Decoction in the intervention of diabetic nephropathy was discussed. Results A total of 1502 subjects were included in 19 RCTs literature. The results of Meta-analysis showed that the treatment group was superior to the control group in terms of effective rate, blood glucose, blood lipid, and renal function index (P < 0.05); A total of 559 chemical components and 2306 potential targets were obtained through online database, including 201 components, 145 targets, and 185 channels, which were closely related to intervention of diabetic nephropathy. It was mainly involved in advanced glycation end products/AGEs receptor (AGE-RAGE) signaling pathway, insulin resistance, tumor necrosis factor (TNF) signaling pathway, mitogen activated protein kinase (MAPK) signaling, and other molecular events. Conclusion Conventional western medicine plus Bushen Huoxue Decoction can improve the clinical effect of diabetic nephropathy and show some advantages in reducing blood sugar, lipid, and protecting renal function, but the overall level of evidence is low, still need large-scale, multi-center RCT for further support; Bushen Huoxue Decoction dry pre diabetic nephropathy is a comprehensive result of multi-component, multi-target interaction, the treatment of diabetic nephropathy is mainly achieved by the intervention of oxidative stress, inflammatory response, polyol pathway, insulin pathway, apoptosis and other ways. This study is a research attempt based on the combination of Meta analysis and network pharmacology, and also provides reference for clinical evaluation and mechanism research of other drugs.

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国家自然科学基金资助项目（81774014）