低血糖对急性心肌梗死后内质网应激介导心肌细胞凋亡的作用和机制研究

Effcet of hypoglycemia on endoplasmic reticulum stress-induced apoptosis of cardiomyocytes after AMI and its mechanism

目的通过体内大鼠模型观察低血糖水平对内质网应激(ERS)感受蛋白及凋亡信号分子表达的影响。方法将Wister大鼠40只中随机选20只结扎左冠状动脉前降支建立大鼠急性心肌梗死(AMI)模型;另20只为假手术,再随机分为正常血糖假手术组(SN组)、正常血糖AMI组(MN组)、低血糖假手术组(SL组)、低血糖AMI组(ML组),每组10只。建立术前低血糖模型,术后24h处死取材,评估大鼠心肌细胞凋亡程度、检测心肌组织中葡萄糖调节蛋白78/免疫球蛋白结合蛋白(GRP78/BIP)、蛋白激酶R样内质网激酶(PERK)和C/EBP同源蛋白(CHOP)及Caspase-12的表达情况。结果 ML组及MN组心肌细胞凋亡指数[(29.36±2.15)%、(20.27±2.80)%]明显高于SN组和SL组[(1.82±0.83)%、(1.97±0.96)%,P<0.05];MN组和ML组GRP78、PERK、CHOP及Caspase-12的表达明显高于SN组和SL组(P<0.01);MN组与ML组PERK表达比较,无统计学差异(P>0.05)。结论 AMI前低血糖水平激活了ERS诱导的细胞凋亡通路;内质网特异性标记蛋白表达与心肌细胞凋亡变化规律一致,ERS通路可能参与了大鼠AMI后心肌细胞凋亡的调控。

Objective To study the effect of hypoglycemia on expression of endoplasmic reticulum stress（ERS）receptive protein and apoptosis signaling molecules in an in vivo animal model.Methods Forty Wister rats were randomly divided into AMI group and sham operation group（20in each group）.The animals were further divided into sham operation group with normal blood glucose（SN group）,AMI group with normal blood glucose（MN group）,sham operation group with hypoglycemia（SL group）,and AMI group with hypoglycemia（ML group）,10 in each group.Apoptosis of cardiomyocytes was assayed.Expressions of GRP78/BIP,PERK,C/EBP and Caspase-12 were detected.Results The apoptotic index of cardiomyocytes was significantly higher in ML and MN groups than in SN and SL groups（29.36% ±2.15% vs 1.82% ±0.83%,20.27% ±2.80%vs 1.97% ±0.96%,P 0.05）.The expression levels of GRP78,PERK,CHOP and Caspase-12 were significantly higher in MN and ML groups than in SN and SL groups（P〈0.01）.Conclusion Hypoglycemia before AMI activates ERS-induced apoptosis of cardiomyocytes and expression of specific endoplasmic reticulum chaperone protein is associated with apoptosis of cardiomyocytes,indicating that the ERS pathway may be involved in regulation of apoptosis of cardiomyocytes after AMI.