螺内酯对大鼠心肌梗死后梗死周边区超极化活化环核苷酸门控通道表达的影响

Effects of Spironolactone on HCN Expression in Infarcted Border Zone after Myocardial Infarction in Rats

目的了解大鼠急性心肌梗死后梗死周边区心肌中HCN2、HCN4的mRNA和蛋白表达变化,探讨螺内酯对心肌梗死后梗死周边区心肌中HCN2、HCN4表达的影响。方法通过开胸结扎冠状动脉左前降支的方法成功建立大鼠心肌梗死模型,心梗后24h存活的12只大鼠随机分为心梗组及螺内酯组,6只假手术组的大鼠仅穿线通过左冠状动脉前降支而不结扎动脉。心肌梗死后一周取心梗大鼠的梗死周边区心肌组织,而假手术组取相对应的心肌组织,用荧光定量PCR方法检测HCN2、HCN4的mRNA水平,用Western blot方法检测HCN2、HCN4的蛋白水平。结果心梗组和螺内酯组较假手术组HCN2、HCN4的mRNA和蛋白表达水平升高,差异有统计学意义(P<0.05),而螺内酯组较心梗组HCN2、HCN4的mRNA和蛋白表达水平下降,差异有统计学意义(P<0.05)。结论急性心肌梗死后1周梗死周边区心肌组织中HCN2和HCN4通道蛋白的表达明显升高,而螺内酯能明显减少急性心肌梗死后梗死周边区心肌组织中HCN2和HCN4通道蛋白的表达。

Objective To investigate the changes in mRNA and protein expression of HCN2 and HCN4 in infarcted bor- der zone after acute myocardial infarction（ AMI） in rats and to discuss effects of Spironolactone on HCN2 and HCN4 expression in infarcted border zone after myocardial infarction. Methods Rat myocardial infarction model was established by ligaturing the left anterior descending coronary artery after thoracotomy. 24 hours after AMI, 12 survival rats were randomly divided into myocardial infarction group and Spironolactone group. 6 rats in sham-operation group were only threaded through the left anterior descending coronary artery but notligatured. One week after AMI, myocardial tissue of infarcted border zone in AMI rats was sampled and in sham-operation group, corresponding parts of myocardial tissue were also sampled, mRNA level of HCN2 and HCN4 was determined by fluorescent quantitative PCR and protein level of HCN2 and HCN4 was determined by Western Blotting. Results mRNA and protein level of HCN2 and HCN4 in Myocardial infarction group and Spironolaetone group was higher than sham-operation group, the difference being statistically significant（ P 〈 0. 05 ） ,and mRNA and protein level of HCN2 and HCN4 in Spironolaetone group was lower than myocardial infarction group, the difference being statistically significant （ P 〈 0. 05 ）. Condusion The expression of HCN2 and HCN4 channel protein in infarcted border zone raised significantly one week after AMI, but Spironolactone can signifi- cantly decrease the expression of HCN2 and HCN4 channel protein in infarcted border zone after AMI.