瑞舒伐他汀对急性心肌梗死大鼠心肌细胞凋亡及胱天蛋白酶-3基因表达的影响

Effect of rosuvastatin on the myocardial apoptosis and the expression of caspase-3 gene in rats with acute myocardial infarction

目的研究瑞舒伐他汀对急性心肌梗死(AMI)大鼠心肌细胞凋亡及胱天蛋白酶-3(caspase-3)基因表达情况的影响。方法雄性健康SD大鼠45只,10只作为假手术组(假手术组仅于左冠状动脉前降支穿线而不作结扎)。另外35只构建急性心肌梗死大鼠模型,建模成功后,将存活的27只模型大鼠随机分为实验组(n=14)及模型组(n=13)。实验组术后第1天开始以1 mg·kg^(-1)·d^(-1)瑞舒伐他汀灌胃,模型组和假手术组术后第1天开始以等量生理盐水灌胃,各组均连续干预1个月。干预后用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测各组大鼠心肌细胞凋亡及心肌梗死情况;用免疫组化法检测各组大鼠心肌组织caspase-3表达情况。结果 TUNEL检测结果显示,模型组心肌细胞呈片状棕褐色,实验组棕褐色着色明显减少,假手术组呈散在少量棕褐色。假手术组、实验组和模型组的心肌细胞凋亡指数分别为2.33±1.10,6.01±3.12,17.13±8.76,实验组和模型组较假手术组均显著升高,但实验组较模型组显著降低(P<0.01)。免疫组化结果显示,假手术组仅有少量棕黄色着色,模型组及实验组棕黄色着色部位明显增多,着色程度明显加重,但实验组不及模型组。假手术组、实验组和模型组的caspase-3蛋白阳性染色指数分别为94.98±13.44,110.67±18.59,138.25±20.93,实验组和模型组较假手术组均显著升高(P<0.05),但实验组较模型组显著降低(P<0.01)。结论瑞舒伐他汀可有效抑制急性心肌梗死模型大鼠心肌细胞凋亡,其作用机制可能与下调心肌组织中凋亡相关调节基因caspase-3的表达相关。

Abstract： Objective To explore the effect of rosuvastatin on the myocardial apoptosis in rats with acute myocardial infarction （AMI） and its influence on the expression of caspase -3 gene. Methods Forty -five healthy male SD rats, 10 of them were sham operation group only ligated with the left anterior descending coronary artery without ligation）, other 35 rats were construct the AMI model, the 27 survival model rats were ran- domly divided into test group （n = 14） and model group （n =13）. Test group was gavaged 1 mg· kg-1 . d-t rosuvastatin from the 1t day post - operation, Model group was gavaged equivalent 0. 9% NaC1 from the 1＂ day post -operation. Each group was intervened for 1 month continuously. The myocardial apoptosis and myocardial infarction of rats in each group were observed by terminal- deoxynucleotidyi transferase mediated nick endlabeling （TUNEL） method, and the caspase -3 gene was compared by immunohistochemistry. Results The TUNEL detec- tion restdts showed that in model group, the myocardial cell was schistose sepia staining, and the sepia staining decreased significantly in test group, and the sham -operation group showed a scattered and bit sepia staining. The apoptotic index （AI） of sham -operation group, test group and model group were 2. 33 ± 1.10, 6. 01 ±3. 12, 17. 13 ±8. 76. Compared with sham-operation group, the AI in test group and model group were significantly increased （P 〈0. 05）, while the test group decreased significantly compared with model group （P 〈 0. 01 ）. The immunohistochemistry detection results showed that, there was a little brown staining in sham -operation group, and the brown staining parts increased signiiqcantly, and the stai- ning power aggravated significantly in test group and model group, but the brown staining parts and staining power in test group were not as good as model group. Compared with sham - operation group （94. 98 ± 13. 44）, the caspase - 3 positive staining index of test group （110. 67 ± 18. 59） and model group （138. 25 ±20. 93） were significantly increased （P 〈0. 05）, but the caspase -3 of test group decreased significantly compared with model group （P 〈0. 01）. Conclusion Rosuvastatin can restrain the myocardial apoptosis of AMI model rats, and the action mechanism may be related to the downregulation of the expression of apoptosis related adjustment gene easpase -3 in cardiac muscle tissue.