氨氯地平对高胆固醇大鼠心肌缺血再灌注时一氧化氮合酶的影响

目的: 探讨高胆固醇血症大鼠心肌缺血 再灌注损伤时氨氯地平对内皮型一氧化氮合酶(eNOS)和诱导型一氧化氮合酶(iNOS)在冠脉血管内皮表达的影响。方法: 雄性Wistar 大鼠分4 组:单纯高胆固醇血症组;氨氯地平组;氨氯地平+N-甲基亚硝基左旋精氨酸甲酯组;氨氯地平+假手术组。大鼠经高胆固醇喂养6 周后,开胸结扎左冠状动脉,缺血30 min 后,行再灌注20 min、2 h。分别用免疫组织化学ABC 法检测冠脉血管内皮eNOS 和iNOS 的表达水平。结果: 缺血前,氨氯地平可显著降低冠脉血管内皮iNOS 表达(P<0.01)。缺血30 min,高胆固醇血症组eNOS、iNOS 表达明显减少(P<0.01),氨氯地平组eNOS 表达上调(P<0.01),iNOS 下调;再灌注20 min 时,高胆固醇血症组冠脉血管内皮表达iNOS 增多,氨氯地平组eNOS、iNOS 表达明显下调;再灌注2 h 时,氨氯地平组NO 水平及eNOS、iNOS表达较高胆固醇血症组轻度降低。各时相点LNAME均可部分阻断氨氯地平对eNOS、iNOS 的效应。结论: 在高胆固醇血症时、缺血期及再灌注早期,氨氯地平可调节eNOS、iNOS 表达,减少心肌缺血再灌注损伤。

Effects of amlodipine on expression of nitric oxide synthase in myocardial ischemia reperfusion model in hypercholesterolemia rats

AIM: To assess the influence of amlodipine on the expression of eNOS and iNOS on coronary vessels in myocardial I R model in hypercholesterolemia rats. METHODS: 64 healthy male Wistar rats were randomly divided into 4 groups:pure hypercholesterolemia group (Con), amlodipine group (AM), amlodipine +L-NAME group (AL), and amlodipine +sham group (Sham).Rats were fed with 3 %-4 % cholesterol and 15 %-20 % lard diet for 6 weeks.As dissecting thorax, the left coronary artery (LCA) was ligated for 30 minutes, and then followed a relaxation for 20 minutes or 2 hours.The expression of iNOS and eNOS was observed by immunohistochemical ABC method on endothelium of coronary vessels. RESULTS: Expression of eNOS and iNOS on endothelium of coronary vessels were marked positive, downregulated after ischemia 30 minutes, apparently increased after reperfusion 20 minutes, and reached the peak after reperfusion 2 hours in Con group.However, the effects were reversed partly by amlodipine.In AM group, the expression of NOS especially iNOS was downregulated significantly before ischemia (P<0.01), and then the expression of eNOS increased (P<0.01) while iNOS decreased (P>0.05) after ischemia 30 minutes.Both the expression of eNOS and iNOS was downregulated at the point of reperfusion 20minutes, followed an increase oparently but weaker than that in Con groups at 2 hours.In combined with L-NAME, the effect of amlodipine on eNOS and iNOS was partly prevented.CONCLUSION: Amlodipine is effective on hypercholesterolemic, myocardial postischemic and early reperfusion damage reduction, and most probably nitric oxide plays a determinant role in this effect.