氨氯地平对缺血再灌注诱导的大鼠心肌细胞损伤的保护作用  

Protective effect of amlodipine on myocardial cell injury induced by ischemia and reperfusion in rats

作　　者：刘慧[1] 李海剑[2] 高传玉[3] 李玉东[4] 陶亚非[2] 毛绍芬[1] 

机构地区：[1]南阳市中心医院特需一科,河南南阳473009 [2]南阳市中心医院肾内科,河南南阳473009 [3]河南省人民医院心内科,郑州450003 [4]南阳市中心医院心内科,河南南阳473009

出　　处：《中国临床药理学杂志》2016年第14期1304-1306,1321,共4页The Chinese Journal of Clinical Pharmacology

基　　金：河南省医学科技攻关基金资助项目(201001011)

摘　　要：目的研究氨氯地平抑制缺血再灌注诱导的心肌细胞损伤。方法 30只Wistar大鼠随机分为假手术组、模型组、实验组,每组10只。模型组及实验组,通过结扎大鼠左冠状动脉前降支,制作心肌缺血再灌注(MIRI)模型。假手术组及模型组,于术后腹腔注射0.9%NaCl 5 m L;实验组,腹腔注射2 mg·kg^(-1)氨氯地平5 m L,连续灌胃给药7 d。以流式双染法检测心肌细胞凋亡情况,用免疫印迹法分析心肌组织中B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)蛋白表达及磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)通路的激活状况,以分光光度法检测天冬氨酸蛋白水解酶3(Caspase 3)活性。结果与假手术组的早期凋亡率(2.34±0.35)%及晚期细胞凋亡率(3.58±0.39)%比较,模型组早期凋亡率(15.69±1.14)%及晚期细胞凋亡率(24.74±2.56)%显著提高(P<0.05)。假手术组的Bax表达量为(0.18±0.01)、Caspase 3活性为(1.00±0.10),模型组的Bax表达量(0.62±0.06)及Caspase 3活性(3.98±0.18)显著提高(P<0.05);假手术组的Bcl-2表达量为(0.99±0.10)、PI3K表达量为(0.89±0.06),模型组的Bcl-2表达量为(0.14±0.01)及PI3K表达量为(0.18±0.01)显著下调(P<0.05);假手术组的AKT磷酸化水平为(0.95±0.10),模型组的AKT磷酸化水平为(0.13±0.01)显著降低(P<0.05)。与模型组比较,实验组的早期凋亡率(5.23±0.13)%,晚期细胞凋亡率(8.09±0.35)%;实验组的Caspase 3活性(1.47±0.14),实验组能扭转此变化(P<0.05)。结论氨氯地平通过激活PI3K/AKT信号通路能抑制缺血再灌注诱导的心肌细胞损伤。Objective To explore inhibition of amlodipine on myocardial cell injury induced by ischemia reperfusion. Methods Thirty Wistar rats were randomly into three groups： sham operation group（ n = 10）,model group group（ n = 10）,test group（ 2 mg · kg^-1amlodipine,n = 10）. The model group and test group were made by ligation of left anterior descending coronary artery to make the model of myocardial ischemia reperfusion. Rats in each group were administered 7 d before ligation. Cell apoptosis was examed by flow dual staining method. The activity of cysteinyl aspartate specific proteinase 3（ Caspase 3） was measured by spectrophotometry. The activation of phosphatidylinositol 3kinase（ PI3K） / protein kinase B（ AKT） signalling pathway,B- celllymphoma- 2（ Bcl- 2）,Bcl- 2 associated X protein（ Bax） were assayed by Western blot. Results Compared to sham operation group on early and late myocardial cell apoptosis,myocardial cell apoptosis with（ 2. 34 ± 0. 35） %,（ 3. 58 ± 0. 39） %,that on early and late myocardial cell apoptosis were increased with（ 15. 69 ± 1. 14） %,（ 24. 74 ± 2. 56） % in model group（ P〈0. 05）. Compared to sham operation group on the activity of Bax with（ 0. 18 ± 0. 01） and Caspase 3 activity with（ 1. 00 ± 0. 10）,the expression of Bax express with（ 0. 62 ± 0. 06） and Caspase 3 activity with（ 3. 98 ± 0. 18） in model group were increased（ P〈0. 05）. Compared to sham operation group on the expre-ssion of Bcl- 2 with（ 0. 99 ± 0. 10） and expression of PI3 K with（ 0. 89 ± 0. 06）,on the expression of Bcl- 2 with（ 0. 14 ± 0. 01） and expression of PI3 K with（ 0. 18 ± 0. 01） in model group were decreased（ P〈0. 05）.Compared to sham operation group on phosphorylation of AKT with（ 0. 95 ± 0. 10）,the phosphorylation of AKT in model group with（ 0. 13 ± 0. 01） was decreased（ P〈0. 05）. Compared with model group,test group could change the variation on the early and late myocardial cell apoptosis with（

关 键 词：氨氯地平 缺血再灌注 心肌细胞凋亡 磷脂酰肌醇3激酶/蛋白激酶B信号通路 

分 类 号：R972[医药卫生—药品]