目的 探讨格列齐特对2型糖尿病大鼠离体心脏缺血预适应保护作用的影响。方法 将造模成功的2型糖尿病大鼠随机分为糖尿病缺血预处理组、糖尿病再灌注损伤组、糖尿病缺血预处理+格列齐特组、糖尿病再灌注损伤+格列齐特组。将对照组大鼠随机分为缺血预处理组、再灌注损伤组。分别于平衡灌注后、缺血再灌注开始及再灌注60 min末3个时间点分别收集冠脉流出液，测定乳酸脱氢酶（LDH）、肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）的释放量；在再灌注末，取左心室游离壁心肌组织，进行荧光定量PCR检测心肌ATP敏感性钾离子（KATP）通道组成亚基Kir6.2和SUR2A mRNA的表达；免疫组织化学技术检测其蛋白的表达水平。结果 对于糖尿病非药物治疗大鼠，糖尿病缺血预处理组与糖尿病再灌注损伤组比较，冠脉流出液中LDH、CK、CK-MB无明显差异；Kir6.2和SUR2A mRNA及蛋白表达也均无明显差异。而与糖尿病缺血预处理组、糖尿病再灌注损伤+格列齐特组比较，糖尿病缺血预处理+格列齐特组均降低了糖尿病大鼠心肌缺血预处理后缺血再灌注损伤冠脉流出液中LDH、CK、CK-MB释放量（P<0.05）；也使Kir6.2 mRNA及蛋白表达明显增加（P<0.05）；但SUR2A mRNA表达差异无统计学意义。与糖尿病再灌注损伤+格列齐特组比较，糖尿病缺血预处理+格列齐特组SUR2A蛋白表达水平也增加明显（P<0.05）。结论 格列齐特对心肌缺血预处理的保护作用无不利影响，反而能改善2型糖尿病大鼠心肌缺血预适应的保护作用。

Objective To evaluate the effect of gliclazide on ischemic preconditioning (IPC) in type 2 diabetic rats. Methods The type 2 diabetic rats were randomly divided into four groups: diabetic ischemic preconditioning (GDI), diabetic reperfusion injury (GDR), diabetic ischemic preconditioning + gliclazide (GDI + Glc), and diabetic reperfusion injury + gliclazide (GDR + Glc) groups. The normal rats also were randomly divided into two groups: ischemic preconditioning (GIP) and reperfusion injury (GIR) groups. Coronary effluent liquid was collected at the end of balance infusion, at the beginning of ischemia reperfusion, and after reperfusion, and the releases of LDH, CK, and CK-MB were detected. At the end of perfusion, the expression levels of Kir6.2 and SUR2A mRNA in the myocardial tissue were measured by fluorescent quantitative PCR method, and the expression levels of Kir6.2 and SUR2A protein were assessed by immunohistochemistry. Results In non-drug diabetic rats, the releases of LDH, CK, and CK-MB in coronary effluent liquid had no significant difference in GDI group compared with GDR group. The expression levels of Kir6.2 and SUR2A mRNA and protein also had no obvious difference. However, compared with GDI and GDR + Glc groups, the releases of LDH, CK, and CK-MB in coronary effluent liquid markedly decreased in GDI + Glc group (P< 0.05). The expression levels of Kir6.2 mRNA and protein in GDI + Glc group were significantly higher than those in GDI and GDR + Glc groups (P< 0.05), but the expression level of SUR2A mRNA had no difference. At the same time, compared with the GDR + Glc group, the expression level of SUR2A protein also significantly increased in GDI + Glc group (P< 0.05). Conclusion Gliclazide has no adverse effect on protection of myocardial IPC. On the contrary, gliclazide can improve ischemic preconditioning in type 2 diabetic rats.

青岛市公共领域科技支撑计划项目（11-2-3-2-（12）-nsh）