井冈山大学学报（自然科学版）

本研究综合运用网络药理学与分子对接及生物信息学等方法，系统揭示全杜仲胶囊干预高血压肾病的“多成分-多靶点-多通路”作用机制。基于中药系统药理学数据库与分析平台（TCMSP）和BATMAN-TCM数据库，设定口服生物利用度（OB≥30%）与类药性（DL≥0.18）为筛选条件，最终筛选出22个源自杜仲的关键活性化合物。利用SwissTargetPrediction平台预测其作用靶点213个；通过GenCards、DisGeNET等疾病数据库获取高血压肾病相关靶点3 025个，利用STRING数据库分析得到127个“成分-疾病”交集靶点，将其导入Cytoscape构建PPI网络，以Degree值>35为阈值筛选出排名前10位的AKT1、MAPK1、IL6、VEGFA等10个核心靶点，GO功能分析获得2 642个条目，KEGG富集分析获得176个条目，并且显著作用于PI3K-Akt、AGE-RAGE及HIF-1信号通路。此外，生物信息学和分子对接实验证实，MAPK1、AKT1和TP53基因的表达存在差异，同时对活性成分槲皮素表现出强大的亲和力。综上所述，本研究结果阐明全杜仲胶囊可通过调控MAPK1、AKT1及TP53基因表达并抑制肾脏细胞凋亡，从而发挥抗高血压肾病效应。预测该作用机制或涉及PI3K-AKT信号通路的调控，为中药复方防治继发性肾损伤提供了新的科学依据。

In this study, network pharmacology, molecular docking and bioinformatics methods were used to systematically elucidate the “multi-component-multi-target and multi-pathway” mechanism underlying the intervention of Quanduzhong capsule in hypertensive nephropathy. Based on the TCMSP and BATMAN-TCM databases, oral bioavailability(OB ≥ 30%) and drug-like properties(DL ≥ 0.18) were defined as screening criteria, and finally 22 key active compounds derived from Eucommia ulmoides were screened. Integrating the SwissTargetPrediction platform, 213 potential targets were predicted; a total of 3,025 targets related to hypertensive nephropathy were retrieved from disease databases such as GenCards and DisGeNET. A total of 127 “component-disease” intersection targets were obtained by STRING database, which were subsequently imported into Cytoscape to construct a PPI network. With the screening threshold set at a degree value > 35, the top 10 core targets such as AKT1, MAPK1, IL6 and VEGFA were identified. GO functional enrichment analysis yielded 2,642 terms, while KEGG enrichment analysis generated 176 entries, and they significantly affected the PI3K-Akt,AGE-RAGE, and HIF-1 signaling pathways. In addition, bioinformatics and molecular docking experiments confirmed that there were differences in the expression of MAPK1, AKT1, and TP53 genes, and these core genes exhibited strong binding affinity to the active component quercetin. In summary, the present study elucidates that Quanduzhong capsule exerts a therapeutic effect against hypertensive nephropathy by regulating the expression of MAPK1, AKT1 and TP53 genes, as well as inhibiting renal cell apoptosis. Its underlying mechanism is predicted to involve the modulation of PI3K-AKT signaling pathway, which provides novel scientific evidence for the prevention and treatment of secondary renal injury with traditional Chinese medicine formulas.