基于网络药理学及实验验证探讨桂枝茯苓丸防治动脉型肺动脉高压的作用机制OA
Exploration on the Mechanism of Guizhi Fuling Pills in Preventing and Treating Pulmonary Arterial Hypertension Based on Network Pharmacology and Experimental Validation
目的 整合网络药理学预测、分子对接及动物实验验证,探索桂枝茯苓丸防治动脉型肺动脉高压(PAH)的作用机制.方法 通过TCMSP数据库筛选桂枝茯苓丸活性成分及其靶点,通过GeneCards、OMIM数据库获取PAH靶点,将药物靶点与疾病靶点取交集,构建蛋白相互作用网络并筛选核心靶点,进行GO和KEGG通路富集分析,将药物关键成分与核心靶点进行分子对接.采用野百合碱诱导肺动脉高压大鼠模型,将40只SD大鼠分为空白组、模型组、西地那非组及桂枝茯苓丸低、高剂量组,每组8只,予相应干预3周,评估大鼠血流动力学及形态学指标,采用qRT-PCR检测大鼠肺组织IL-1β、IL-6、IL-17A、TNF-α mRNA表达.结果 经数据库检索并筛选获得桂枝茯苓丸药物靶点213个,PAH疾病靶点9 706个,交集靶点192个.桂枝茯苓丸治疗PAH的核心通路为IL-17信号通路,分子对接显示关键活性成分与核心靶点IL1B、IL6、TNF的结合能均小于-5.0 kcal/mol.动物实验结果显示,与空白组比较,模型组大鼠右心室收缩压升高、右心室肥厚,表现出明显肺血管重构(P<0.05),肺组织IL-1β、IL-6、IL-17A、TNF-α mRNA表达显著升高(P<0.000 1);与模型组比较,桂枝茯苓丸高剂量组右心室收缩压显著降低,右心室肥厚减轻,肺血管重构改善,肺组织IL-1β、IL-6、IL-17A、TNF-α mRNA表达降低(P<0.01,P<0.001,P<0.000 1).结论 桂枝茯苓丸可能通过调控IL-17信号通路改善肺血管重构,发挥防治PAH作用.
Objective To explore the mechanism of Guizhi Fuling Pills in preventing and treating pulmonary arterial hypertension(PAH)by integrating network pharmacology prediction,molecular docking,and animal experimental validation.Methods The active components of Guizhi Fuling Pills and their targets were screened through the TCMSP database.PAH targets were obtained from GeneCards and OMIM databases.The intersection of drug targets and disease targets was performed to construct a protein-protein interaction network and screen core targets.GO and KEGG enrichment analyses were conducted,and molecular docking was performed between key components of the drug and core targets.A monocrotaline-induced pulmonary hypertension rat model was established.Totally 40 SD rats were divided into control group,model group,sildenafil group,and Guizhi Fuling Pills low-and high-dosage groups,with 8 rats in each group.After 3 weeks of intervention,hemodynamic and morphological indices were evaluated,and qRT-PCR was used to detect the relative expressions of IL-1β,IL-6,IL-17A,and TNF-α mRNA in lung tissues.Results A total of 213 drug targets of Guizhi Fuling Pills and 9 706 disease targets of PAH were retrieved and screened,with 192 intersection targets identified.The core pathway of Guizhi Fuling Pills in treating PAH was the IL-17 signaling pathway.Molecular docking showed that the binding energies of the key active components with core targets IL1B,IL6 and TNF were all less than-5.0 kcal/mol.Animal experimental results showed that compared with the control group,rats in the model group exhibited elevated right ventricular systolic pressure and right ventricular hypertrophy,with obvious pulmonary vascular remodeling,the expressions of IL-1β,IL-6,IL-17A and TNF-α mRNA in lung tissues of rats in the model group significantly increased(P<0.000 1).Compared with the model group,right ventricular systolic pressure was significantly reduced in the Guizhi Fuling Pills high-dosage group,right ventricular hypertrophy was alleviated,pulmonary vascular remodeling was improved,the expressions of IL-1β,IL-6,IL-17A and TNF-α mRNA in lung tissues decreased(P<0.01,P<0.001,P<0.000 1).Conclusion Guizhi Fuling Pills may improve pulmonary vascular remodeling and exert preventive and therapeutic effects on PAH by regulating the IL-17 signaling pathway.
陆天逊;郑培永;鹿振辉;顾元烨;崔洁;马双双
上海中医药大学附属龙华医院,上海 200032上海中医药大学附属龙华医院,上海 200032上海中医药大学附属龙华医院,上海 200032上海中医药大学附属龙华医院,上海 200032上海中医药大学附属龙华医院,上海 200032上海中医药大学附属龙华医院,上海 200032
医药卫生
动脉型肺动脉高压桂枝茯苓丸网络药理学IL-17信号通路
pulmonary arterial hypertensionGuizhi Fuling Pillsnetwork pharmacologyIL-17 signaling pathway
《中国中医药信息杂志》 2026 (8)
6-13,8
国家自然科学基金面上项目(82374349)国家自然科学基金青年科学基金项目(82505469)上海中医药大学科技发展项目(24KFL053)
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