过氧化物酶体增殖物激活受体γ协同刺激因子1α在早期缺血预处理中的作用  

The Effects of Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α On Early Ischemic Preconditioning

作　　者：韩劲松[1] 阎德民[1] 汪曾炜[2] 朱洪玉[2] 

机构地区：[1]中国医科大学附属第一医院心脏外科,沈阳110001 [2]沈阳军区总医院心血管外科,沈阳110001

出　　处：《中国胸心血管外科临床杂志》2008年第4期281-284,共4页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

基　　金：辽宁省教育厅高等学校科学研究基金资助项目(05L467)~~

摘　　要：目的探讨过氧化物酶体增殖物激活受体γ协同刺激因子1α(PGC-1α)在早期缺血预处理中的作用和早期缺血预处理的机制。方法取Wistar大鼠30只,建立离体心脏Langendorff灌注模型,随机分成3组,每组10只。对照组(CON组):全心灌流120min,不做任何处理;缺血-再灌注组(I/R组):心脏平衡灌流30min后,缺血30min,再灌注60min;缺血预处理组(IPC组):心脏平衡灌流10min,经2次缺血5min复灌5min后,缺血30min,再灌注60min。采用链霉素抗生物素蛋白-过氧化物酶(S-P法)检测PGC-1α的表达,测定平均积分光密度值(IODA);采用电子显微镜对心肌线粒体进行Flameng评分。结果IPC组PGC-1α表达(IODA10.94±5.23)明显高于I/R组(IODA3.88±1.72)和CON组(IODA3.39±2.46;P=0.009,0.007)。I/R组线粒体水肿、破裂明显,而CON组、IPC组线粒体损伤较轻。Flameng评分分析显示,IPC组(0.44±0.13)和CON组(0.88±0.22)线粒体评分低于I/R组(1.78±0.14;P=0.003,0.014)。结论IPC能明显减轻线粒体损伤,其机制与PGC-1α激活和高度表达有关,PGC-1α可能是一种重要的内源性心肌保护物质。Objective To investigate the effect of peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） on early ischemic preconditioning （IPC） which may act as an important role in early IPC. Methods Building isolated working rat heart Langendorff model, thirty Wistar rats were divided randomly into three groups. Control group （CON group, n=10）： a 120-min perfusion was performed without any intervension; ischemia and reperfusion group （I/R group, n=10）： a 30-min equilibration period perfusion, a 30-min ischemia and a 60-min reperfusion were performed. ; IPC group （n=10）： a 10 min equilibration period perfusion was performed, then was elicited by two cycles of 5-min of ischemia interspersed with 5 min reperfusion prior to 30 min ischemia and a 60 min reperfusion. Frozen sections of myocardium at cardiac apex were made and immunohistochemical staining was used to detect expression and the intergrated optical density average （IODA） of PGC-1α. Uhrathin sections were made and the mitochondria under each specimen was evaluated according to Flameng score. Results PGC-la expression in IPC group （IODA 10.94±5.23） was significantly higher than that in I/R group （IODA 3.88±1.72） and that in CON group （IODA 3.39±2.46; P=0.009, 0.007）. The mitochondria changes in I/R group were significant edema and severe damage; but there were not so severe in CON group and IPC group. Flameng score of IPC group （0.44±0.13） and CON group （0. 88±0.22） were lower than that in I/R group （1.78±0.14; P=0.003, 0. 014） respectively. Conclusion IPC can protect myocytes mitochondria from ischemia and reperfusion. The cardioprotection may be related with the activation and the high expression of PGC-1α, which may act as one of the most important endogenous defence factors of the heart.

关 键 词：缺血预处理 线粒体 缺血-再灌注 过氧化物酶体增殖物激活受体γ协同刺激因子1α 

分 类 号：R541[医药卫生—心血管疾病]