目的 探讨芪参益气滴丸对腹主动脉缩窄大鼠的肾保护效应和机制。方法 通过网络药理学筛选芪参益气滴丸活性成分及肾损伤靶点，构建“中药-成分-靶点-疾病”网络和蛋白质-蛋白质相互作用（PPI）网络，并进行分子对接；采用腹主动脉缩窄复制压力超负荷大鼠模型，随机分为假手术组、模型组、缬沙坦组、芪参益气滴丸组。药物干预8周后检测肾功能指标、肾组织病理及纤维化标志物变化。结果 筛选芪参益气滴丸活性成分124个，药物-疾病共同靶点203个；关键活性成分为槲皮素、木犀草素、山柰酚、丹参酮Ⅱ_A等，核心靶点为AKT1、TNF、IL-6等；基因本体（GO）注释及京都基因与基因组百科全书（KEGG）通路富集分析显示PI3K-Akt通路、AGE-RAGE、MAPK通路等是潜在的作用环节；分子对接证实丹参酮Ⅱ_A与核心靶点结合亲和力强；与模型组比较，芪参益气滴丸干预能够降低腹主动脉缩窄大鼠血清肌酐、尿素氮水平及24 h尿蛋白含量（P<0.05、0.01），显著改善大鼠肾功能；肾脏胶原容积分数亦明显降低（P<0.01），且抑制转化生长因子β1（TGF-β1）、结缔组织生长因子（CTGF）蛋白表达（P<0.01），减轻肾纤维化。结论 芪参益气滴丸具有多成分、通过多靶点、作用多环节发挥肾脏保护效应，其机制可能与抑制TGF-β1、CTGF表达相关。

Objective To investigate the renoprotective effects and mechanisms of Qishen Yiqi Dropping Pills in rats with abdominal aortic constriction. Methods The active ingredients of Qishen Yiqi Dropping Pills and targets associated with kidney injury were screened using network pharmacology, which was also used to build “TCM-component-target-disease” networks, protein-protein interaction networks, and molecular docking; Abdominal aortic constriction was used to create a pressure overload rat model, which was then randomly assigned to four groups: sham operation, model, valsartan, Qishen Yiqi Dropping Pills, and. Renal function indicators, renal histology, and fibrosis markers were evaluated following an 8-week medication intervention. Results A total of 124 active components of Qishen Yiqi Dropping Pills were tested, and 203 common drug-disease targets were found. Key active components were quercetin, luteolin, kaempferol, and tanshinone Ⅱ_A, with main targets such as AKT1, TNF, and IL-6. GO functional and KEGG enrichment studies identified the PI3K-Akt, AGE-RAGE, and MAPK pathways as probable mechanisms of action. Molecular docking confirmed a significant binding affinity between tanshinone Ⅱ_A and the key targets. Qishen Yiqi Dropping Pills effectively lowered serum creatinine, blood urea nitrogen levels, and 24 h urine protein content in rats with abdominal aortic constriction（P＜0.05, 0.01）, leading to improved renal function. Renal collagen volume fraction decreased significantly（P＜0.01）, whereas TGF-β1 and CTGF protein expression were suppressed（P＜0.01）, resulting in reduced renal fibrosis. Conclusion Qishen Yiqi Dropping Pills exert renoprotective effects through multiple components acting on multiple targets and pathways, with mechanisms potentially related to inhibition of TGF-β1 and CTGF expression.

R285.5

国家自然科学基金项目(81603559); 苏州工业园区东方华夏心血管健康研究院--力·心中药科研创新基金项目(2024-CCATCM-005)