目的 基于网络药理学方法及实验验证探讨复方金钱草颗粒 （JQC） 对前列腺增生 （BPH） 的防治作用及机制。方法 （1） 通过 TCMSP 数据库检索广金钱草、车前草、光石韦、玉米须的活性成分，同时通过文献检索进行补充；利用 PubChem、Swiss Target Prediction、CTD 数据库筛选 JQC 活性成分作用靶点。通过 GeneCards、CTD、DRUGBANK、DisGeNET 数据库筛选 BPH 疾病相关靶点。对 JQC 活性成分作用靶点与 BPH 疾病相关靶点进行映射取交集，即得 JQC 治疗 BPH 的潜在作用靶点。利用 STRING 11.5 数据库对 JQC 治疗 BPH 的潜在作用靶点进行蛋白互作 （PPI） 网络分析。利用 Metascape 平台对潜在作用靶点进行 GO 功能及 KEGG 通路富集分析。采用 Cytoscape 3.9.1 软件构建“药物-成分-靶点-通路”网络，预测 JQC 治疗 BPH 的关键活性成分及核心靶点。利用 AutoDock Vina 软件进行关键活性成分与核心靶点的分子对接验证。 （2） 将 60 只 SD 雄性大鼠随机分为空白组、模型组、前列舒通胶囊组 （0.324 g•kg-1） 及 JQC 高、中、低剂量组 （3.24、1.62、0.81 g•kg-1） ，每组10 只。采用去势联合注射丙酸睾酮诱导建立 BPH 大鼠模型。灌胃给药，每天 1 次，连续给药 30 d。摘取大鼠前列腺组织，称定质量并计算前列腺湿质量指数；采用 ELISA 法检测血清 COX-2、VEGF、PGE2 的含量；HE染色法观察大鼠前列腺组织的病理变化；Western Blot 法检测前列腺组织中 AKT1、p-AKT1、PI3K、p-PI3K、COX-2、VEGF 蛋白表达水平。结果 （1） 共得到 JQC 活性成分作用靶点 260 个，疾病相关靶点 1 584 个，JQC治疗 BPH 的潜在作用靶点 （交集靶点） 125 个。PPI 网络分析发现 AKT1、TNF、TP53、IL1β、EGFR、CASP3、PTGS2 等靶点可能是 JQC 治疗 BPH 的重要靶点。JQC 治疗 BPH 的潜在作用靶点主要与 IL-17、HIF-1、TNF及 PI3K-Akt 通路相关。得到关键活性成分为木犀草素、芹菜素、车前子苷、芒果苷、夏佛塔苷、异牡荆苷，核心靶点为 PTGS2、AR、CASP3、IL6、PTGS1、AKT1 等。共有 24 对“关键活性成分-核心靶点”的分子结合能均≤-6 kcal•mol-1；PTGS2 蛋白受体与木犀草素、芹菜素等配体结合活性最好；AKT1 与车前子苷、芒果苷、木犀草素、芹菜素、夏佛塔苷、异牡荆苷等均具有较好的亲和力。 （2） 与模型组比较，JQC 高、中剂量组大鼠的前列腺湿质量与湿质量指数均明显降低 （P＜0.05，P＜0.01） ；大鼠前列腺腺体基底细胞肥大有明显缓解，腺腔大小相对规则，上皮细胞增生情况均有所改善；血清 COX-2、VEGF、PGE2 水平明显降低 （P＜0.05，P＜0.01） ；前列腺组织中的 p-AKT1、p-PI3K、PI3K、COX-2、VEGF 蛋白表达明显下调 （P＜0.05，P＜0.01） 。结论 JQC 对 BPH 具有明显防治作用，其机制可能是通过车前子苷、芒果苷、木犀草素等活性成分来调控PI3K/Akt 信号通路，抑制 COX-2 的表达，减少 PGE2 释放，进而导致 VEGF 表达下调，抑制前列腺细胞增殖。

Objective To investigate the preventive and therapeutic effect of Compound Jinqiancao Granules （JQC）on benign prostatic hyperplasia （BPH） and its underlying mechanisms using network pharmacological methods for prediction and animal experiments for verification. Methods （1） The active ingredients of Desmodii Stryracifolii Herba， Plantaginis Herba， Herb of Balt Pyrrosia and Corn Silk were retrieved from TCMSP database， and the literature search was conducted for supplement. The targets of the active ingredients in JQC were screened by using PubChem，Swiss Target Prediction and CTD database. GeneCards，CTD，DRUGBANK and DisGeNET database were used to select BPH-related targets. The potential targets of JQC in treating BPH were obtained through taking the intersection of the targets of the active ingredients in JQC and BPH-related targets. PPI network analysis of potential targets for JQC in treating BPH was performed by using STRING 11.5 database. Metascape platform was used to analyze the GO function and KEGG pathway enrichment of potential targets for JQC in treating BPH. “Drug-ingredients-targets-pathway” network was constructed by using Cytoscape 3.9.1 to predict the key targets for JQC in treating BPH. AutoDock Vina software was used for molecular docking validation between key active ingredients and core targets.（2）A total of 60 male rats were randomly divided into control group，model group，Qianlie Shutong Capsules（0.324 g•kg-1）group，JQC high-，medium-，and low- dose（3.24，1.62，0.81 g•kg-1）groups，with 10 rats in each group. BPH rat model was induced by castration combined with injection of testosterone propionate. The corresponding drug was administered orally once a day for 30 consecutive days. Rat prostate tissue was removed and weighted，then the prostate wet mass index was calculated. The content of COX-2，VEGF and PGE2 in serum was detected by ELISA. HE staining was used to observed pathological changes in rat prostate tissue. The protein expression of AKT1，p-AKT1，PI3K，p-PI3K，COX-2 and VEGF in prostate tissue was measured by Western Blot. Results （1） A total of 260 targets of the active ingredients in JQC，1 584 BPH-related targets，and 125 potential targets of JQC in treating BPH were found. PPI results found that AKT1，TNF，TP53，IL1β，EGFR，CASP3 and PTGS2 may be important targets for JQC in treating BPH. The potential targets for JQC in treating BPH are mainly related to IL-17，HIF-1，TNF，and PI3K-AKT pathways. The key active ingredients，such as luteolin，apigenin，plantain asiatica glycoside，mangiferin，shafotaxin and isovitexin， as well as the core targets including PTGS2， AR， CASP3， IL6， PTGS1 and AKT1， were obtained. The molecular binding energies of 24 pairs of “key active ingredients-core targets” were less than or equal to -6 kcal•mol-1. It was found that PTGS2 protein receptor had good binding activity to ligands such as luteolin and apigenin. AKT1 has good affinity with plantain asiatica glycoside， mangiferin， isobutyricin， luteolin， apigenin，shaftaside and isovitexin. （2） Compared with model group，the wet mass and wet mass index of the prostate in JQC high- and medium- dose groups were significantly decreased （P＜0.05，P＜0.01）. Basal cell hyperplasia of the prostate gland in rats was found to be significantly alleviated. The size of the glandular cavity was relatively regular，and the proliferation of epithelial cells had improved. The levels of COX-2，PGE2 and VEGF in the serum were significantly decreased（P＜0.05，P＜0.01）. The protein expression of p-AKT1，p-PI3K，PI3K，COX-2 and VEGF in prostate tissue were significantly down-regulated （P＜0.05，P＜0.01）. Conclusion This study preliminary clarified that JQC has a preventive and therapeutic effect on BPH，and its mechanism is related to active ingredients （plantago asiatica glycoside，mangiferin，and luteolin） -mediated regulation of PI3K-AKT pathway，inhibition of the expression of COX-2， and reduction of PGE2 release， thereby resulting in the down-regulation of VEGF expression and the inhibition of the proliferation of prostate cells.

R285.5；R857.3

中国科学院服务网络计划（STS计划）区域重点项目（KFJ-STS-QYZD-2021-03-004）；广西壮族自治区科技计划项目（桂科AB22035077）