普罗布考对心肌梗死大鼠心肌组织Bcl-2和Bax表达及氧化应激的影响  

Effects of Probucol on Expression of Bcl-2,Bax and Oxidative Stress in Myocardial Infarcted Rats

作　　者：周淑娴[1] 张玉玲[1] 周艳[1] 雷娟[1] 

机构地区：[1]中山大学附属第二医院心血管内科,广东广州510120

出　　处：《中华高血压杂志》2008年第10期907-911,共5页Chinese Journal of Hypertension

摘　　要：背景心肌梗死后心肌细胞凋亡与氧化应激有关,普罗布考为脂溶性强抗氧化剂,实验证明具有保护心肌细胞的作用,该药保护心肌细胞的作用是否通过调控细胞凋亡相关基因 Bcl-2和 Bax 目前尚不清楚。目的研究普罗布考对心肌梗死大鼠心肌组织 Bcb-2和 Bax 表达及氧化应激的影响。方法将心肌梗死后24 h 存活大鼠41只随机分为2组:盐水组(5 mL/d,n=20),普罗布考组[60 mg/(kg·d),n=21],灌胃给药;另设假手术组(n=12)作对照。分别于心肌梗死后6周:导管法测定左室有创血流动力学指标,TUNEL 法检测非梗死区心肌细胞凋亡;RT-PCR 的方法观察心肌组织 Bcl-2及 Bax mRNA 表达的变化;Western blot 检测心肌 Bcl-2及 Bax 蛋白表达;比色法测定心肌组织氧化代谢指标。结果 (1)与假手术组相比,所有心肌梗死大鼠均出现显著的 Bcl-2 mRNA 及蛋白表达降低,Bax mRNA 及蛋白表达与心肌细胞凋亡指数显著升高(P 均<0.01)。与盐水组相比,普罗布考组心肌组织 Bcl-2 mRNA 及蛋白表达显著升高,Bax mRNA 及蛋白表达及心肌细胞凋亡指数显著降低(P 均<0.01);(2)与假手术组相比,所有心肌梗死大鼠心肌组织均出现显著的 MDA 升高,SOD、TAOC 含量及 SOD/MDA 比值降低(P 均<0.01);与盐水组相比,普罗布考组 MDA 显著下降,SOD、TAOC 含量及 SOD/MDA 均升高(P 均<0.01);心肌细胞凋亡指数与 TAOC、SOD/MDA 比值呈负相关(P 均<0.01)。结论心肌梗死后心肌细胞凋亡增加,普罗布考治疗可以抑制心肌细胞凋亡,降低心肌梗死后心肌组织的氧化应激。Background Cardiomyocytes apoptosis was related to oxidative stress which has been shown to play an important role in ventricular remodeling after myocardial infarction （MI）. Probucol is a hypolipidemic and antioxidant agents. Several reports demonstrated its cardioprotective effect after MI. However, the exact effect of probucol on the modification of the apoptosis related gene Bcl-2 and Bax is not clear. Objective To investigate the effects of probucol on mRNA and protein expression of Bcl-2, Bax and oxidative stress in myocardial infarcted rats. Methods Forty-one SD rats that survived 24 h after ligating left anterior descending coronary artery were randomly to receive placebo-saline （5 mL/d, n=20） or probucol （probucol 60 mg/kg · d, n=21）. Twelve rats underwent sham operation were served as control（n = 12 ）. Six weeks after treatment, hemodynamic pararmeters and left ventricular function were measured with catheterization. Cardiomyocytes apoptosis were determined by TUNEL method. Myocardium mRNA of Bcl-2 and Bax expression levels in the non-infarcted myocardium were assessed by RT-PCR. The myocardium protein expression of Bcl-2 and Bax in the non-infarcted myocardium were determined by Western blot. Colorimetry was used to determine oxidative metabolism index in myocardium. Results 1 ）Compared with the sham rats, all MI rats showed marked decrease in Bcl-2 mRNA and protein expression in myocardium with increase of Bax mRNA and protein expression and apoptosis index （P〈0.01, respectively）. Compared with placebo rats, probucol increased Bcl-2 mRNA and protein expression, decreased Bax mRNA and protein expression and apoptosis index （P〈0.01, respectively）. 2）Compared with the sham rats, all MI rats showed marked increase in MDA, and decrease in SOD, TAOC and SOD/MDA ratio （P〈0.01, respectively）. Probucol decreased MDA with concomitantly increased SOD, TAOC and SOD/MDA ratio （P〈0.01, respectively）. Myocardium apoptosis index was negatively correlated with TAOC and SOD/

关 键 词：心肌梗死 凋亡 氧化应激 普罗布考 

分 类 号：R542.22[医药卫生—心血管疾病]