半胱氨酸蛋白酶-3及-9表达上调介导糖尿病大鼠心肌细胞凋亡及抗氧化剂α-硫辛酸的保护作用

Up-regulation of caspase-3 and -9 value expressions participates in hyperglycemia induced-myocardial apoptosis in diabetic rats and the protection of a-lipoic acid

目的探讨天冬氨酸特异性的半胱氨酸蛋白酶（caspase）表达上调对高血糖诱导的心肌细胞凋亡的影响及抗氧化剂α-硫辛酸的防治效果。方法链脲佐菌素（STZ）建立糖尿病大鼠动物模型，实验动物分为糖尿病组、对照组、α-硫辛酸组，分第4周、第8周、第12周3个阶段进行观察。免疫组化染色测定糖尿病大鼠心脏caspase-3、-9mRNA和蛋白质表达的变化。结果糖尿病组第4周、第8周、第12周大鼠心脏caspase-3、-9mRNA和蛋白质表达均高于对照组（P〈0．05），随病程延长两者表达增加（P〈0．05），两者表达变化趋势一致；与糖尿病组比较，α-硫辛酸组在各时间段Caspase-3、-9mRNA和蛋白质表达均下降（P〈0．05）。结论高血糖可以诱导caspase-3、-9表达的增加从而导致心肌细胞的凋亡，抗氧化剂可以下调caspase-3、-9表达，减弱心肌细胞的凋亡。

Objectives To explore the effects of the up-regulation of caspases on high glucose induced myocardial apoptosis and observe the protection value of antioxidant -lipoic acid. Methods Diabetic rat model was induced by a single dose of streptozotocin （45 mg/kg ） and was randomly divided into 3 groups： normal control, diabetes control and -LA. Each group included 3 time points （4, 8 and 12 weeks）. Expressions of caspase-3, -9 mRNA and protein were determined by RT-PCR and immunohistochemistry （IH）respectively. Results Compared with control group, expressions of easpase-3 ,-9 mRNA gradually increased from 4 weeks to 12 weeks in DM group. The content protein of caspase-9, -3 was in accordance with their mRNA expressions. Compared with control group, expressions of caspase-3,-9 mRNA and protein decreased in -LA group. Conclusion High glucose could up-regulate the caspase-9, -3 mRNA and protein resulting in myocardial apoptosis. Antioxidant -LA could down-regulate expressions of caspase-3,-9 mRNA attenuating myocardial apoptosis.