摘要
目的探讨缺血后处理对心肌肥厚大鼠离体心脏缺血再灌注损伤的影响及其信号机制。方法通过腹主动脉结扎建立大鼠心肌肥厚模型,用Landendorff装置建立心肌肥厚大鼠离体心脏缺血再灌注模型。观察缺血后处理对心肌肥厚大鼠离体缺血再灌注心脏左心室收缩压,冠状动脉流量,肌酸磷酸激酶和乳酸脱氢酶释放,心肌梗死范围,心肌组织中蛋白激酶B/Akt(Akt)、糖原合成酶激酶-3β(GSK-3β)磷酸化的影响。结果与缺血再灌注对照组相比,缺血后处理组心脏左心室收缩压、冠状动脉流量显著高,冠状动脉循环流出液中肌酸磷酸激酶、乳酸脱氢酶含量低,心肌梗死范围减小,心肌组织中磷酸化Akt(Ser473)、磷酸化GSK-3β(Ser9)水平高,磷脂酰肌醇-3激酶(PI3K)抑制剂渥曼青霉素(wortmannin)能够抑制缺血后处理所致的磷酸化Akt(Ser473)、磷酸化GSK-3β(Ser9)水平升高,但只能部分消除缺血后处理的心脏保护效应。结论缺血后处理能够减轻心肌肥厚大鼠离体心脏缺血再灌注损伤,P13K/Akt/GSK-3β信号途径参与介导缺血后处理对离体缺血再灌注肥厚心肌的保护作用。
Objective To explore the effects of ischemie postconditioning on isehemia/reperfusion injury in isolated hypertrophied rat heart and investigate the signal transduction pathway changes induced by ischemia postconditioning. Methods Cardiac hypertrophy was induced in rats by abdominal aortic banding, and isolated hypertrophied rat heart ischemia/reperfusion model was made by Langendorff technique to evaluate the effects of ischemia postconditioning on left ventricular systole pressure, coronary artery flow, creatine phosphokinase （CPK） and lactate dehydrogenase （LDH） release, myocardial infarction size, and the level of myocardial phospho-protein kinase B/Akt （Ser473）, phospho-glycogen synthase kinase-3β （Ser9）. Following groups were studied （n = 12 each group） ： IR, 30 min ischemia （I）/60 min Reperfusion （R） ; Post： 30 min ischemia, 6 circles of 10 s I/10 s R followed by 60 min R; PostWort： 30 min ischemia, 6 circles of 10 s I/10 s R, wortmannin （ 10^-7 mol/L） followed by 60 min R; Wort： 30 min ischemia, wortmannin （ 10^-7 mol/L） followed by 60 min R. Results Left ventricular systolic pressure and coronary artery flow were significantly increased, myocardial infarction size and the release of CPK, LDH significantly reduced in Post group compared to that in IR group. Phospho-protein kinase B/Akt （Ser473） and phospho-glycogen synthase kinase-3β （Ser9） levels were also significantly higher in Post group than that in IR group. Phosphatidylinositol 3-kinase （PI3K） inhibitor wortmannin prevented the increase of phospho-protein kinase B/Akt （Ser473） and phospho-glyeogen synthase kinase-3β（Set9） induced by isehemie posteonditioning, but only partly abolished the eardioprotection of ischemie posteonditioning. Conclusion Isehemie posteonditioning attenuates ischemia/reperfusion injury in isolated hypertrophied rat heart. The eardioprotective effects of isehemie posteonditioning were partly mediated through PI3K/Akt/GSK-3β signaling pathway.
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2006年第8期685-689,共5页
Chinese Journal of Cardiology
基金
广东省自然科学基金资助项目(5001675)
关键词
再灌注损伤
心肌
信号传导
缺血后处理
Reperfusion injury
Myocardium
Signal transduction
Ischemia postconditioning
