基于网络药理学及实验验证探究丹参治疗低氧性肺动脉高压的机制  

Exploring the Mechanism of Salvia Miltiorrhiza in the Treatment of Hypoxic Pulmonary HypertensionBased on Network Pharmacology and Experimental Validation

作　　者：董政委 张敏[1] 赵换 邢作英[1] 于瑞[1] 樊官伟[3,4] 王永霞[1] 朱明军[1] DONG Zhengwei;ZHANG Min;ZHAO Huan;XING Zuoying;YU Rui;FAN Guanwei;WANG Yongxia;ZHU Mingjun(The First Affiliated Hospital of Henan University of Chinese Medicine,Heart Center/National Regional(Tra-ditional Chinese Medicine)Cardiovascular Diagnosis and Treatment Center,Zhengzhou 450000,China;Tianjin University of Traditional Chinese Medicine,College of Chinese Medicine,Tianjin 301617,China;The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin Key Laboratory of Tradi-tional Chinese Medicine Prescription and Syndrome Transformation,Tianjin 300193,China;Tianjin Universi-ty of Traditional Chinese Medicine,National Clinical Research Center for Acupuncture and Moxibustion of Tra-ditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]河南中医药大学第一附属医院,心脏中心/国家区域(中医)心血管诊疗中心,河南郑州450000 [2]天津中医药大学中药学院,天津301617 [3]天津中医药大学第一附属医院天津市中医方证转化研究重点实验室,天津300193 [4]天津中医药大学国家中医针灸临床医学研究中心,天津301617

出　　处：《世界科学技术-中医药现代化》2024年第8期2023-2029,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：河南省国家中医药传承创新中心科研专项(2023ZXZX1130):丹参酮IIA靶向结合DYRK1A介导PKA/TFAM通路抗肺动脉高压血管重塑的机制研究,负责人:董政委。

摘　　要：目的基于丹参有效治疗低氧联合Su5416诱导低氧型肺动脉高压(Hypoxic pulmonary hypertension,HPH)的前期基础,探究丹参治疗HPH的机制。方法 采用网络药理学的方法,收集丹参活性成分,获取活性成分的作用靶点,收集HPH疾病靶点,获取丹参成分靶点和HPH疾病靶点交集,构建蛋白质相作网络(Protein-protein interaction networks,PPI),并通过KEGG分析,获得丹参治疗HPH的关键通路。使用分子生物学的方法对关键通路进行验证。结果 通过网络药理学获得81个丹参治疗HPH的靶点,PPI显示药物成分-疾病共同核心靶点包括ATK1、TNF、EGFR、IL6、ESR1,KEGG富集通路主要包括PI3K-AKT signaling pathway、HIF-1 signaling pathway、MAKP signaling pathway、TNF signaling pathway以及JAK-STAT signaling pathway等。分子生物学检测显示丹参具有降低HySu-PH小鼠肺组织纤维化和抑制PI3K/AKT信号通路的作用。结论 丹参具有减轻HPH肺纤维化的作用,其作用机制与抑制PI3K/Akt信号通路有关。Objective Based on the pre-existing basis of effective treatment of hypoxia combined with Su5416-induced hypoxic pulmonary hypertension(HPH)by Salvia miltiorrhiza,to investigate the mechanism of Salvia miltiorrhiza in the treatment of HPH.Methods Using a network pharmacology approach to obtain the key pathways of Salvia miltiorrhiza for the treatment of HPH.The active ingredients of Salvia miltiorrhiza were collected to obtain the targets of the active ingredients.HPH disease targets were collected to obtain the intersection of Salvia miltiorrhiza component targets and HPH disease targets.Protein-Protein Interaction Networks(PPIs)were constructed and KEGG analysis was performed to obtain the key pathways of Salvia miltiorrhiza for HPH.Then used molecular biology to validate the key pathways.Results The 81 targets of Salvia miltiorrhiza for the treatment of HPH were obtained by network pharmacology,and PPI showed that drug component-disease common core targets included ATK1,TNF,EGFR,IL6,ESR1,and KEGGenriched Pathway mainly included PI3K-AKT signaling pathway,HIF-1 signaling pathway,MAKP signaling pathway,TNF signaling pathway,JAK-STAT signaling pathway and so on.Molecular biological assays showed that Salvia miltiorrhiza had the effect of reducing lung tissue fibrosis and inhibiting the PI3K/AKT signalling pathway in HySu-PH mice.Conclusion Salvia miltiorrhiza has the effect of attenuating pulmonary fibrosis,and its mechanism of action is related to the inhibition of the PI3K/Akt signalling pathway.

关 键 词：丹参 网络药理学 低氧型肺动脉高压 肺纤维化 PI3K/AKT信号通路 

分 类 号：R285[医药卫生—中药学]