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30min后 ,行再灌注 2 0min、2h。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 .0 1)。缺血 30min ,高胆固醇血症组eNOS、iNOS表达明显减少 (P <0 .0 1) ,氨氯地平组eNOS表达上调 (P <0 .0 1) ,iNOS下调 ;再灌注 2 0min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 2h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L NAME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 20 minutes, 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.