基于非靶向蛋白质组学的心脉通片治疗难治性高血压机制研究  

Mechanism of Xinmaitong Tablets against Resistant Hypertension Based on Untargeted Proteomic Analysis

作　　者：杜建民 张晨宁 张星海 张文玉 赵恒利 温清 DU Jianmin;ZHANG Chenning;ZHANG Xinghai;ZHANG Wenyu;ZHAO Hengli;WEN Qing(Clinical Research Center,Central Hospital Affiliated to Shandong First Medical University,Ji’nan Shandong 250000,China)

机构地区：[1]山东第一医科大学附属中心医院临床研究中心,山东济南250000

出　　处：《中国药物警戒》2024年第11期1270-1275,共6页Chinese Journal of Pharmacovigilance

基　　金：济南市科技计划(202134049);山东省自然科学基金资助项目(ZR2021QH343)。

摘　　要：目的基于非靶向蛋白质组学分析方法探讨心脉通片活性成分对难治性高血压的潜在作用机制。方法收集难治性高血压(RH)和控制性高血压(CH)患者的临床样本,基于非靶向蛋白质组学技术,表征两组患者人群血浆中的差异蛋白;利用TCMSP数据库和PharmMapper数据库检索心脉通片的活性成分及作用靶点;运用Metascape数据库进行基因本体(GO)及京都基因与基因组百科全书(KEGG)通路富集分析。筛选出药物与在难治性高血压患者中差异表达蛋白的交集靶点,利用MOE软件进行分子对接验证。结果共获得心脉通片活性成分162个,药物与难治性高血压差异表达蛋白的交集靶点2个。心脉通片治疗高血压的关键活性成分为黄芩苷、菠菜甾醇、木犀草素、山柰酚、槲皮素、豆固醇以及β-谷甾醇;核心靶点为肽基-脯氨酰顺式-反式异构酶A(PPIA)、热休克蛋白HSP90-alpha(HSP90AA1)。GO&KEGG富集分析涉及前20条信号通路,包括血小板脱颗粒、中性粒细胞脱颗粒、炎症反应信号通路等。分子对接显示关键活性成分与核心靶点之间有良好的结合活性。结论心脉通片可能通过黄芩苷作用于PPIA发挥对难治性高血压的治疗作用。Objective To explore the potential mechanism by which the active ingredients of Xinmaitong tablets combat resistant hypertension using untargeted proteomic analysis methods.Methods Clinical samples were collected from patients with resistant hypertension(RH)and controlled hypertension(CH)respectively.Using untargeted proteomic technology,differential proteins in plasma from the two groups of patients were characterized.The active ingredients and targets of Xinmaitong tablets were retrieved from the TCMSP and PharmMapper databases.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using the Metascape database.Intersection targets of the drug with differentially expressed proteins in RH patients were identified,and molecular docking validation was conducted using the MOE software.Results A total of 162 active ingredients from Xinmaitong tablets were obtained,and 2 intersection targets between the drug and differentially expressed proteins in resistant hypertension were identified.The key active ingredients of Xinmaitong tablets for treating hypertension were baicalin,spinasterol,luteolin,kaempferol,quercetin,stigmasterol,andβ-sitosterol while the core targets were Peptidyl-prolyl cis-trans isomerase A(PPIA)and heat shock protein HSP 90-alpha(HSP90AA1).GO and KEGG enrichment analysis involved the top 20 signaling pathways,including platelet degranulation,neutrophil degranulation,and inflammatory response signaling pathways.Molecular docking showed good binding activity between the key active ingredients and the core targets.Conclusion Xinmaitong tablets may exert their therapeutic effect against resistant hypertension by acting on PPIA through baicalin.

关 键 词：心脉通片 黄芩苷 菠菜甾醇 难治性高血压 非靶向蛋白质组学 分子对接 机制 疗效 

分 类 号：R972[医药卫生—药品]