伊伐布雷定对冠心病大鼠心肌损伤的保护作用

Protective effect of ivabradine on myocardial injury in rats with coronary heart disease

目的观察伊伐布雷定对冠心病大鼠心肌损伤的保护作用。方法20只大鼠通过高脂饲料喂养及注射垂体后叶素模拟冠心病,并将造模成功大鼠随机分为模型组及伊伐布雷定组[10 mg(kg·d)],另外设立假手术组大鼠正常饲料喂养,连续给药12周。测定大鼠心脏功能、心肌细胞凋亡指数(AI)、丙二醛(MDA)含量、超氧化物岐化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活性,肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6含量及核因子-κB(NF-κB)信号通路相关蛋白表达。结果与模型组比较,伊伐布雷定组左室收缩压(LVSP)、+dp/dtmax、-dp/dtmax上升(P<0.01),AI[(8.35±0.84)%比(36.35±3.68)%]降低(P<0.01),TNF-α[(4.83±0.48)μg/L比(14.57±1.46)μg/L]、IL-1β[(74.68±7.49)ng/L比(245.32±24.53)ng/L]及IL-6[(97.28±9.73)μg/L比(221.43±20.68)μg/L]、MDA[(63.82±6.33)μmol/g比(84.36±8.44)μmol/g]含量减少(P<0.01),SOD[(6.29±0.39)U/g比(2.78±0.25)U/g]、CAT[(12.56±1.26)U/g比(8.31±0.83)U/g]、GSH-Px[(14.47±1.45)U/g比(25.34±2.57)U/g]活性提高(P<0.01),p-IκBα(0.24±0.02比0.88±0.09)及p-NF-κB p65(0.32±0.03比0.72±0.07)表达量下调(P<0.01)。结论伊伐布雷定可能通过抗氧化及抗炎作用抑制冠心病大鼠心肌损伤。

Objective To explore protective effect of ivabradine on myocardial injury in rats with coronary heart disease.Methods Twenty rats were fed with high-fat diet and injected with Pituitrin to simulate coronary heart disease.Successful rats were randomly divided into model group and ivabradine group[10 mg/(kg·d)].In addition,rats in sham operation group were fed with normal diet,continuous administration for 12 weeks.Cardiac function,apoptotic index(AI),the level of malondialdehyde(MDA),the activity of superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px),the level of tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,IL-6,and the expression of nuclear factor-κ-gene bindingκ(NF-κB)signal pathway related protein was detected.Results Compared with the model group,LVSP、+dp/dtmax、-dp/dtmax was increased(P<0.01),AI[(8.35±0.84)%vs.(36.35±3.68)%],the contents of TNF-α[(4.83±0.48)μg/L vs.(14.57±1.46)μg/L],IL-1β[(74.68±7.49)ng/L vs.(245.32±24.53)ng/L,IL-6[(97.28±9.73)μg/L vs.(221.43±20.68)μg/L]and MDA[(63.82±6.33)μmol/g vs.(84.36±8.44)μmol/g]was decreased(P<0.01),the activities of SOD[(6.29±0.39)U/g vs.(2.78±0.25)U/g],CAT[(12.56±1.26)U/g vs.(8.31±0.83)U/g]and GSH-Px[(14.47±1.45)U/g vs.(25.34±2.57)U/g]was increased(P<0.01),and the expressions of p-IκBα(0.24±0.02 vs.0.88±0.09)and p-NF-κB p65(0.32±0.03 vs.0.72±0.07)was decreased in dexamethasone group(P<0.01).Conclusion Ivabradine might inhibit myocardial injury in rats with coronary heart disease through antioxidant and anti-inflammatory effects.