目的 基于网络药理学、分子对接及实验验证探讨肾康注射液治疗慢性肾小球肾炎的作用机制。方法 基于前期表征的肾康注射液的主要化学成分、文献中报道的定量成分、药典中含量测定的成分及TCMSP数据库筛选活性成分，以Swiss TargetPrediction在线网站为主，以PharmMapper在线网站为辅获得各活性成分的作用靶点，并与通过文献挖掘及多种数据库查找的慢性肾小球肾炎相关靶点进行对比，得到肾康注射液治疗慢性肾小球肾炎的关键靶点，借助Metascape在线网站对得到的关键靶点进行基因本体（GO）富集分析和京都基因和基因百科全书（KEGG）通路注释分析，并进行分子对接和动物实验验证。结果 共筛选到17个肾康注射液主要活性成分（芦荟大黄素、羟基红花黄色素A、大黄素甲醚、山柰酚等），对应568个靶点，活性成分靶点与疾病靶点取交集得到关键靶点112个。这些成分主要作用于蛋白激酶B1（Akt1）、雌激素受体1（ESR1）、基质金属蛋白酶-9（MMP-9）、白细胞介素（IL）-2等核心靶点，涉及胞内磷脂酰肌醇激酶（PI3K）/Akt、丝裂原活化蛋白激酶（MAPK）等主要信号通路；分子对接结果显示，肾康注射液的主要活性成分与核心靶点都有较好的结合活性。动物实验结果表明，与模型组相比，肾康注射液各剂量组均可以改善大鼠的毛发、体质量和肾功能（P＜0.05）；显著降低大鼠尿液样本中的尿蛋白、ACR值，血液样本中的肌酐、尿素氮含量，大鼠肾组织中肿瘤坏死因子-α（TNF-α）、IL-6、IL-1β含量以及Akt1、ESR1、MMP-9、IL-2的蛋白表达水平（P＜0.05、0.01、0.001）。结论 肾康注射液治疗慢性肾小球肾炎主要作用于Akt1、ESR1、MMP-9、IL-2等靶点，参与PI3K/Akt、MAPK、TNF等信号通路的调节，体现了中药多成分、多靶点、多通路的协同作用特点。

Objective To investigate the mechanisms of Shenkang Injection in treatment of chronic glomerulonephritis by using network pharmacology, molecular docking and experimental validation. Methods The main chemical constituents of Shenkang Injection were identified based on previously observed components, literature-reported quantitative components and pharmacopoeia-determined content levels, and TCMSP database. The action targets of each active ingredient were obtained mainly through the Swiss TargetPrediction online website and supplemented by the PharmMapper online website. They were compared with the targets related to chronic glomerulonephritis found through literature mining and multiple databases to obtain the key targets of Shenkang Injection in treatment of chronic glomerulonephritis. The key targets obtained were subjected to GO enrichment analysis and KEGG pathway annotation analysis through the Metascape online website, and molecular docking and animal experiments were conducted for verification. Results A total of 17 main active ingredients (aloe emodin, hydroxysafflower yellow pigment A, emodin methyl ether, kaempferol, etc) of Shenkang Injection were screened out, corresponding to 568 targets. By taking the intersection of the active ingredient targets and the disease targets, 112 key targets were obtained. These components mainly act on core targets such as Akt1, ESR1, MMP-9, and IL-2, involving major signaling pathways such as PI3K/Akt and MAPK. The results of molecular docking showed that the main active ingredients of Shenkang Injection all had good binding activity with the core targets. The results of animal experiments showed that compared with the model group, each dose group of Shenkang Injection could improve the hair, body weight and renal function of rats (P < 0.05), significantly reduced the values of urine protein and ACR in rat urine samples, the contents of creatinine and urea nitrogen in blood samples, the contents of TNF-α, IL-6, IL-1β in rat renal tissues, and the protein expression levels of Akt1, ESR1, MMP-9, and IL-2 (P< 0.05, 0.01, 0.001). Conclusion Shenkang Injection in treatment of chronic glomerulonephritis mainly acts on targets such as Akt1, ESR1, MMP-9, and IL-2, and participates in the regulation of signaling pathways such as PI3K/Akt, MAPK, and TNF, demonstrating the collaborative characteristics of multi-component, multi-target, and multi-pathway effects of traditional Chinese medicine.

R287.3

国家自然科学基金项目（82104515）；河南省高等学校重点科研项目（26A360023）；河南省医学科技攻关计划项目（LHGJ20210283）