极化液对缺血/再灌大鼠心肌细胞死亡及心脏功能的影响:胰岛素的关键作用

目的　探讨葡萄糖 胰岛素 钾极化液 (GIK)对心肌缺血 /再灌 (MI/R)后心肌细胞死亡(坏死和凋亡 )及心脏功能的影响 ,并比较和分析GIK各组分在其中的作用。方法　制备大鼠MI/R模型 ,分别用生理盐水、GIK、葡萄糖 钾液 (GK)或胰岛素干预分组。观察动脉血压、血糖、左室压等的变化 ,再灌注结束后检测心肌梗死或提取DNA检测心肌细胞凋亡。结果　MI/R造成明显的心脏功能障碍、心肌梗死和缺血区细胞凋亡。GIK与胰岛素 (而非GK)具有相似的减轻再灌注心肌损伤作用 ,包括减少心肌梗死范围 (41 3± 8 3) %和 (39 6± 8 6) %比对照组 (54 4± 1 0 4) % ,q =4 34和q=4 90 ,P值均 <0 0 5]、减弱DNA梯带形成及促进再灌后心脏收缩 /舒张功能恢复。结论　GIK可减少心肌梗死、促进缺血心脏功能恢复 ,胰岛素可能通过抑制缺血心肌细胞凋亡在GIK心肌保护中发挥关键作用。

Effects of glucose-insulin-potassium cocktail on cardiac myocyte death and post-ischemic recovery cardiac functional recovery: the critical role of insulin

OBJECTIVE: To study the effect of glucose-insulin-potassium (GIK) cocktail on cardiac myocyte death (i.e., necrosis and apoptosis) and cardiac functional recovery following myocardial ischemia/reperfusion (MI/R), and to further investigate the role of insulin in the GIK-induced cardioprotective effect. METHODS: Male Sprague-Dawley rats were subjected to 30 min myocardial ischemia followed by reperfusion for 4 h (for cardiac function and cardiomyocyte apoptosis study) or 6 h (for myocardial infarction measurement). Anesthetized rats were randomly treated with continuous infusions of saline, GIK (Glucose: 200 g/L, Insulin: 60 U/L and KCl: 60 mmol/L), GK or insulin at 4 ml.kg(-1).h(-1), beginning 5 min before reperfusion and continuing through the 4-h reperfusion. Arterial blood pressure, ECG and left ventricular pressure were monitored throughout the experiment. Myocardial DNA fragmentation and myocardial infarction were determined at the end of reperfusion. RESULTS: MI/R caused significant cardiac dysfunction and myocardial death (both necrosis and strong DNA ladder formation). Compared with the vehicle treated rats, the GIK-treated rats showed protection against MI/R injury as evidenced by reduced myocardial infarction (41.3 +/- 8.3)% vs. (54.4 +/- 10.4)% of vehicle, P < 0.05, n = 10], marked decrease of DNA fragmentation, and improved recovery of cardiac systolic/diastolic function at the end of reperfusion left ventricular developed pressure: (94 +/- 6) mm Hg vs. (86 +/- 5) mm Hg of vehicle, P < 0.05; +LVdP/dt(max): (2 940 +/- 114) mm Hg/s vs. (2 733 +/- 132) mm Hg/s, P < 0.05; -LVdP/dt(max): (2 629 +/- 156) mm Hg/s vs. (2 463 +/- 133) mm Hg/s, P < 0.05]. Insulin exerted the similar cardioprotective effects with GIK; whereas the rats receiving GK failed to show any significant, cardioprotection against MI/R injury. CONCLUSIONS: GIK exerts cardioprotective effect against postischemic myocardial injury. Insulin, mainly through its anti-apoptotic effect, plays a critical role in the GIK-elicited myocardial protection in MI/R.