曲美他嗪对心肌缺血再灌注大鼠的冠状动脉微循环内皮屏障的保护作用机制研究  

Protective Effects of trimetazidine on endothelial barrier of coronary microcirculation in myocardial ischemia-reperfusion rats

作　　者：刘刚[1] 孙海霞[2] 魏秀玲[3] LIU Gang;SUN Hai-xia;WEI Xiu-ling(Department of Cardiovascular Surgery,Qinghai Provincial People's Hospital,Xining 810000,Qinghai Province,China;Department of Cardiovascular Ultrasound,Qinghai Provincial People's Hospital,Xining 810000,Qinghai Province,China;Department of Neurosurgery,Qinghai Provincial People's Hospital,Xining 810000,Qinghai Province,China)

机构地区：[1]青海省人民医院心脏大血管外科,青海西宁810000 [2]青海省人民医院心血管超声科,青海西宁810000 [3]青海省人民医院神经外科,青海西宁810000

出　　处：《中国临床药理学杂志》2022年第13期1471-1475,共5页The Chinese Journal of Clinical Pharmacology

基　　金：青海省科技厅基金资助项目(2020-ZJ-777)。

摘　　要：目的探讨曲美他嗪预处理对心肌缺血再灌注冠状动脉微循环内皮障碍(CDM)的影响。方法构建大鼠心肌缺血再灌注模型,将成功建立模型的大鼠按照体重分为模型组和实验组;假手术组大鼠开胸暴露心脏后只穿线不结扎,每组10只动物。实验组于术前2周及术前2 h予以10 mg·kg^(-1)·d^(-1)曲美他嗪灌胃,假手术组、模型组予以等量生理盐水灌胃。用酶联免疫吸附法检测大鼠血清活性氧簇(ROS)、内皮素-1(ET-1)、一氧化氮(NO)含量,用实时荧光定量-聚合酶链反应法和蛋白质印迹法分别检测心脏组织中核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)mRNA和蛋白水平。结果假手术组、模型组、实验组大鼠血清ROS表达量分别为(100.63±15.69),(233.03±36.77)和(150.63±15.69)μmol·L^(-1);这3组ET-1表达量分别为(153.28±22.99),(269.60±40.55)和(198.28±22.99)ng·L^(-1);这3组NO表达量分别为(15.53±2.33),(8.75±1.66)和(11.69±2.33)μmol·L^(-1);这3组心脏组织中Nrf2 mRNA表达水平分别为1.00±0.15,0.37±0.05和0.80±0.12;这3组HO-1 mRNA表达水平分别为1.01±0.15,0.43±0.06和0.78±0.12。上述指标,模型组与假手术组相比,或实验组与模型组相比,差异均有统计学意义(均P<0.05)。心脏组织中Nrf2蛋白表达水平与其mRNA水平表达趋势一致。结论曲美他嗪预处理可能通过促进Nrf2/HO-1通路活化,抑制ROS、ET-1表达,促进NO表达,对心肌缺血再灌注冠状动脉微循环内皮屏障具有保护作用。Objective To investigate the effect of trimetazidine preconditioning on coronary microcirculatory endothelial dysfunction(CDM)after myocardial ischemia and reperfusion.Methods The myocardial ischemia-reperfusion model was established in rats.The successful model rats were divided into model group and experimental group according to body weight.In the sham operation group,rats were exposed to the heart after thoracotomy and only sutured without ligation,with 10 animals in each group.The experimental group was given intragastric administration of 10 mg·kg^(-1)·d^(-1) trimetazidine 2 weeks and 2 h before operation,and the sham operation group and the model group were given intragastric administration of the same amount of normal saline.The levels of reactive oxygen species(ROS),endothelin-1(ET-1)and nitric oxide(NO)in serum were detected by enzyme-linked immunosorbent assay.The mR NA and protein levels of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in heart tissue were detected by real-time fluorescence quantitative polymerase chain reaction and Western blotting,respectively.Results The expression of ROS in serum of rats in sham operation group,model group and experimental group were(100.63±15.69),(233.03±36.77)and(150.63±15.69)μmol·L^(-1),respectively.The expression levels of ET-1 in these three groups were(153.28±22.99),(269.60±40.55)and(198.28±22.99)ng·L^(-1),respectively.The expression levels of NO in these three groups were(15.53±2.33),(8.75±1.66)and(11.69±2.33)μmol·L^(-1),respectively;the expression levels of Nrf2 mR NA in these three groups were 1.00±0.15,0.37±0.05and 0.80±0.12,respectively;the expression levels of HO-1 mR NA in these three groups were 1.01±0.15,0.43±0.06 and 0.78±0.12,respectively.The above indicators were significantly different between the model group and the sham operation group,or between the experimental group and the model group(all P<0.05).The expression of Nrf2 mR NA and Nrf2 protein in heart tissue showed the same trend.Conclusion The effe

关 键 词：曲美他嗪 心肌缺血再灌注 冠状动脉微循环内皮屏障 核因子E2相关因子2/血红素加氧酶-1通路 

分 类 号：R97[医药卫生—药品]