摘要
目的:探讨胰岛素(Insulin)后处理对离体大鼠心肌的保护作用及其可能机制。方法:将32只Wistar大鼠随机分成4组,对照组(Control组),缺血再灌注组(I/R组),低剂量胰岛素后处理组(L-POST组),高剂量胰岛素后处理组(H-POST组),每组8只。Control组开胸取左心室肌作为缺血前对照;I/R组、L-POST组、H-POST组建立离体心脏Langendorff-Neely灌注模型,预灌注K-H缓冲液30min后,灌注4℃STH-2心脏停搏液,停搏心脏并低温维持30min,复灌K-H缓冲液60min后,取左心室肌备用;L-POST组和H-POST组于复灌期给予含胰岛素的K-H液灌注。采用免疫组化和Western blot分别检测大鼠心肌内皮型一氧化氮合酶(Endothe lial nitric oxide synthase,eNOS)、蛋白激酶C(Proteinkinase C,PKC)的分布和量的变化;TUNEL法检测心肌细胞凋亡指数(Apoptotic index,AI)。结果:与Control组相比,I/R组、L-POST组、H-POST组内皮型一氧化氮合酶(Endothelial nitric oxide synthase,eNOS)、蛋白激酶C(Protein kinase C,PKC)表达量明显增多(P<0.05),AI明显增高(P<0.05);与I/R组相比,L-POST组和H-POST组eNOS、PKC表达量明显增加(P<0.05),AI明显减少(P<0.05);与L-POST组相比,H-POST组eNOS、PKC表达量增加(P<0.05),AI明显减少(P<0.05)。结论:胰岛素后处理具有减轻心肌缺血/再灌注损伤的作用,其机制可能与增加eNOS、PKC表达,抑制细胞凋亡有关,高剂量胰岛素对缺血/再灌注心肌细胞较低剂量胰岛素具有更显著的保护作用。
Objective：To explore the effects and mechanisms of insulin postconditioning on myocardial protection in isolated rat hearts.Methods：32 Wistar rats were randomly divided intocontrol group,ischemia/reperfusion group（I/R group）,low dose insulin postconditioning group（L-POST group）and high dose insulin postconditioning group（H-POST group）,with 8 rats in each group.Langendorff and neely perfusion models were steadily established,then the rat hearts were arrested by cardioplegia（St.Thomas No.2 solution,STH-2）after perfusion for 30 min.These arrested hearts were remained for 30 min at 4℃and then underwent reperfusion for 60 min.In L-POST group and H-POST group,the arrested hearts were reperfused by Krebs-Henseleit buffer solution（K-H）with insulin.The content changes of myocardial eNOS and PKC were detected by immunohistochemistry and Western blo（tWB）,the AI（Apoptosis index,AI）of cardiomyocyte was detected by TUNEL.Results：Compared with control group,higher expression of eNOS and PKC and higher AI were detected in I/R group、L-POST group and H-POST group （P0.05）;compared with I/R group,higher expression of eNOS and PKC and lower AI were detected in L-POST group and H-POST group（P0.05）;compared with L-POST group,higher expression of eNOS and PKC,and lower xpression of AI were detected in H-POST group（P0.05）.Conclusion：The insulin postconditioning could protect heart from myocardial ischemia/reperfusion injury,which might be associated with increased eNOS,PKC,and inhibited apoptosis.The effect of high dose insulin postconditioning is better than that of the low dose.
出处
《重庆医科大学学报》
CAS
CSCD
北大核心
2010年第8期1163-1166,共4页
Journal of Chongqing Medical University
