目的 探討格列齊特對2型糖尿病大鼠離體心臟缺血預(yù)適應(yīng)保護作用的影響。方法 將造模成功的2型糖尿病大鼠隨機分為糖尿病缺血預(yù)處理組、糖尿病再灌注損傷組、糖尿病缺血預(yù)處理+格列齊特組、糖尿病再灌注損傷+格列齊特組。將對照組大鼠隨機分為缺血預(yù)處理組、再灌注損傷組。分別于平衡灌注后、缺血再灌注開始及再灌注60 min末3個時間點分別收集冠脈流出液，測定乳酸脫氫酶（LDH）、肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）的釋放量；在再灌注末，取左心室游離壁心肌組織，進行熒光定量PCR檢測心肌ATP敏感性鉀離子（KATP）通道組成亞基Kir6.2和SUR2A mRNA的表達(dá)；免疫組織化學(xué)技術(shù)檢測其蛋白的表達(dá)水平。結(jié)果 對于糖尿病非藥物治療大鼠，糖尿病缺血預(yù)處理組與糖尿病再灌注損傷組比較，冠脈流出液中LDH、CK、CK-MB無明顯差異；Kir6.2和SUR2A mRNA及蛋白表達(dá)也均無明顯差異。而與糖尿病缺血預(yù)處理組、糖尿病再灌注損傷+格列齊特組比較，糖尿病缺血預(yù)處理+格列齊特組均降低了糖尿病大鼠心肌缺血預(yù)處理后缺血再灌注損傷冠脈流出液中LDH、CK、CK-MB釋放量（P<0.05）；也使Kir6.2 mRNA及蛋白表達(dá)明顯增加（P<0.05）；但SUR2A mRNA表達(dá)差異無統(tǒng)計學(xué)意義。與糖尿病再灌注損傷+格列齊特組比較，糖尿病缺血預(yù)處理+格列齊特組SUR2A蛋白表達(dá)水平也增加明顯（P<0.05）。結(jié)論 格列齊特對心肌缺血預(yù)處理的保護作用無不利影響，反而能改善2型糖尿病大鼠心肌缺血預(yù)適應(yīng)的保護作用。

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.

青島市公共領(lǐng)域科技支撐計劃項目（11-2-3-2-（12）-nsh）