基于网络药理学及动物实验探讨心脉佳制剂抑制高血压心肌肥大的作用机制  

Exploring the mechanism of Xin Mai Jia in inhibiting hypertensive cardiac hypertrophy based on network pharmacology and animal experiments

作　　者：雷程静 于淼 李艳格 唐小光 赵繁荣[1,2,3] 祝田田 LEI Chengjing;YU Miao;LI Yange;TANG Xiaoguang;ZHAO Fanrong;ZHU Tiantian(School of Pharmacy,Xinxiang Medical College,Xinxiang 453500,Henan,China;Henan International Joint Laboratory of Cardiovascular Reconstruction and Drug Intervention,Xinxiang 453500,Henan,China;Xinxiang Key Laboratory of Cardiovascular Reconstruction Intervention and Molecular Targeted therapy,Xinxiang 453500,Henan,China)

机构地区：[1]新乡医学院药学院,河南新乡453500 [2]河南省心血管重塑与药物干预国际联合实验室,河南新乡453500 [3]新乡市血管重塑介入与分子靶向治疗药物开发重点实验室,河南新乡453500

出　　处：《中国临床药理学与治疗学》2025年第1期32-41,共10页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金(81800051);河南省科技公关项目(212102310319)。

摘　　要：目的:通过网络药理学及动物实验探讨心脉佳制剂(XinMaiJia,XMJ)抑制高血压心肌肥大的作用机制。方法:通过检索TCMSP数据库及相关文献报道收集XMJ有效成分及作用靶点;利用Gene Cards、OMIM、Drug Bank数据库筛选高血压心肌肥大靶点;构建中药-活性成分-潜在靶点网络和蛋白质-蛋白质相互作用(PPI)网络;使用DAVID软件进行靶点基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析;使用AutoDock软件进行分子对接。建立高血压大鼠(SHR)模型,采用HE染色检测心肌组织形态及细胞肥大情况,Masson染色检测心肌组织胶原沉积表达,蛋白免疫印迹法(Westernblot)检测心肌组织中热休克蛋白(HSP90AA1)、哺乳动物雷帕霉素(mTOR)、过氧化物酶体增殖因子活化受体γ(PPARG)、肿瘤坏死因子(TNF-α)表达情况。结果:共检索到XMJ中潜在活性成分56个,获得高血压心肌肥大相关靶点5492个,核心网络中的靶点按照Degree值进行排名,筛选到4个主要靶点:HSP90AA1、mTOR、PPARG、TNF-α。HE染色结果显示,与正常组比较,SHR组大鼠心肌细胞平均面积显著增加(P<0.05),XMJ组心肌细胞平均面积无显著变化,SHR+XMJ组心肌肥大显著缓解(P<0.05)。Masson染色结果显示,与正常组比较,SHR组大鼠间质纤维化、血管旁纤维化水平明显上升(P<0.01),XMJ则可明显降低SHR组大鼠纤维化水平(P<0.01)。Western blot结果显示,相较于正常组大鼠,SHR组大鼠心肌组织HSP90AA1、PPARG表达下调,mTOR磷酸化下调,TNF-α显著上调(P<0.01);SHR+XMJ组大鼠心肌组织HSP90AA1、PPARG、TNF-α表达恢复至正常水平,mTOR磷酸化恢复正常水平;而XMJ组,相较于正常组大鼠上述指标无明显变化。结论:XMJ抑制高血压心肌肥大的作用机制可能通过多成分-多靶点-多通路的综合作用实现。AIM:To exploring the mechanism of Xin Mai Jia(XMJ)in inhibiting hypertensive cardiac hypertrophy through network pharmacology and animal experiments.METHODS:Retrieving the active ingredients and target points of XMJ by searching the TCMSP database and related literature reports;using the Gene Cards,OMIM,and Drug Bank databases to screen targets for hypertensive cardiac hypertrophy;constructing a network of traditional Chinese medicine-active ingredients-potential targets and a protein-protein interaction(PPI)network;using DAVID software for target gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis;using Auto Dock software for molecular docking.A spontaneously hypertensive rat(SHR)model was established,and hematoxylin-eosin(HE)staining was used to detect the morphology of cardiac tissue and cellular hypertrophy,Masson staining was used to detect collagen deposition in cardiac tissue,and Western blot to detect the expression of heat shock protein(HSP90AA1),mammalian target of rapamycin(mTOR),peroxisome proliferator-activated receptorγ(PPARG),and tumor necrosis factor(TNF-α)in cardiac tissue.RESULTS:A total of 56 potential active ingredients were identified in XMJ,and 5,492 targets related to hypertensive cardiac hypertrophy were obtained.The targets in the core network were ranked according to their Degree values,and four main targets were selected:HSP90AA1,mTOR,PPARG,and TNF-α.The results of HE staining showed that compared with the normal group,the average area of cardiomyocytes in the SHR group increased significantly(P<0.05),while there was no significant change in the XMJ group.The hypertrophy in the SHR+XMJ group was significantly alleviated(P<0.05).The results of Masson staining showed that compared with the normal group,the levels of interstitial fibrosis and perivascular fibrosis in the SHR group rats increased significantly(P<0.01),and XMJ could significantly reduce the fibrosis levels in the SHR group rats(P<0.01).The results of

关 键 词：网络药理学 分子对接 心脉佳制剂 心肌肥大 核心靶点 

分 类 号：R965.2[医药卫生—药理学]