Omapatrilat对大鼠心肌梗死后心肌炎性细胞及心室重构的影响  

Effects of omapatrilat on the expression of inflammatory cell and ventricular remodeling after myocardial infarction in rats

作　　者：邹军 石峰 袁凤新 杨玲 黄景文 罗韶金 罗长军 ZOU Jun;SHI Feng;YUAN Feng-xin;YANG Ling;HUANG Jing-wen;LUO Shao-jin;LUO Chang-jun(Department of Cardiology,Foshan Nanhai District People′s Hospital,Foshan,Guangdong 528200,China;Department of Radiology,Gongan County Hospital of Traditional Chinese Medicine,Gongan,Hubei 434300,China;Department of Cardiology,Afficiated Liutie Central Hospital of Guangxi Medical University,Liuzhou,Guangxi 545000,China)

机构地区：[1]佛山市南海区人民医院心血管内科,广东佛山528200 [2]公安县中医医院放射科,湖北公安434300 [3]广西医科大学附属柳铁中心医院心血管内科,广西柳州545000

出　　处：《岭南心血管病杂志》2019年第1期112-117,共6页South China Journal of Cardiovascular Diseases

基　　金：广东省医学科学技术研究基金项目(项目编号:A2018482);广西卫计委项目(项目编号:Z2016271);佛山市医学类科技攻关项目(项目编号:2017AB000162);佛山市科技创新项目(项目编号:2017AG100102)

摘　　要：目的探讨血管肽酶抑制剂omapatrilat对大鼠心肌梗死(myocardial infarction,MI)后心肌炎性细胞及心室重构的影响。方法建立大鼠经典急性MI模型,将实验小鼠随机分组为假手术组、MI组和omapatrilat干预MI组。其中Omapatrilat干预MI组为术后24 h予omapatrilat 40 mg.kg^(-1)·d^(-1)给药MI大鼠,而假手术组和MI组给予纯净水处理。术后第4周时通过Masson氏染色法检测心肌胶原容积分数以及心肌血管周围胶原面积;TUNEL染色法检测大鼠非梗死区心肌细胞凋亡指数;Western blot法检测细胞因子肿瘤坏死因子-α(tumor necrosisfactor,TNF-α)、白细胞介素-10(interleukin-10,IL-10)的蛋白表达。结果与假手术组比较,MI组非梗死区心肌组织炎性细胞因子TNF-α蛋白表达明显增加,差异有统计学意义(P<0.05);抗炎细胞因子IL-10蛋白表达量无明显变化,差异无统计学意义(P>0.05);胶原沉积增加、心肌细胞凋亡数量明显增多,差异有统计学意义(P<0.01)。与假手术组比较,omapatrilat干预MI组TNF-α蛋白表达减少、IL-10蛋白表达增加,差异有统计学意义(P<0.05)。而在非梗死区,omapatrilat干预MI组的心肌细胞凋亡数量以及胶原沉积均较MI组明显降低,差异有统计学意义(P<0.01)。结论 omapatrilat可显著改善大鼠急性MI后的心室重构,其发挥作用的机制很可能与减轻心肌炎症反应相关,同时还可能涉及非MI心肌间质胶原沉积的减少以及抗心肌细胞凋亡作用。Objectives To investigate the effects of vasopeptidase inhibitor(omapatrilat)on ventricular remodelling,expression of inflammatory cell after myocardial infarction(MI)in rats.Methods Male SD rats were randomly divided into sham,MI and MI+omapatrilat group.MI was produced by ligation of the left anterior descending coronary artery.After 24 hours of operation,rats in the MI+omapatrilat group were treated with 40 mg·kg-1·d-1 omapatrilat in their drinking water,and rats in the sham and MI groups were treated with placebo.Four weeks after MI,the collagen volume fraction(CVF)and the perivascular collagen volume area(PVCA)were measured with Masson staining.The cardiomyocyte apoptosis in the noninfarcted zone were determined with TUNEL staining.The expressions of tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)were detected with Western blot.Results Four weeks after MI,the expression of TNF-αprotein in the noninfarcted zone of MI groups was greater than that of sham group(P<0.05),and IL-10 protein expression had no significant change in the noninfarcted zone(P >0.05).CVF、PVCA and the number of cardiomyocyte apoptotic in the noninfarcted zone of MI group significantly increased while compared with those of sham group(P<0.01).Compared with MI group,expression of suppressed IL-10 protein could be upreguated,while that of TNF-αprotein decreased by omapatrilat intervention after MI(P<0.05).CVF、PVCA and the number of cardiomyocyte apoptotic in the groups of omapatrilat intervention lowered significantly(P<0.01).Conclusions The vasopeptidase inhibitor shows favorable effects on left ventricular remodeling after MI in rats,it might be because of omapatrilat partially inhibit TNF-αactivation,reduce collagen deposition and help anti-apoptosis in myocardial cells.

关 键 词：心肌梗死 心肌炎症 血管肽酶抑制剂 

分 类 号：R542.22[医药卫生—心血管疾病]