Gao Feng, Shi Dong-wei, Wang Xiao-ming, Dong Ling, Wang Yue-min, Ma Xin-liang
Department of Physiology, The Fourth Military Medical University, Xi'an 710032, China.
Zhonghua Nei Ke Za Zhi. 2003 Mar;42(3):148-52.
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.
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.
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.
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.
研究葡萄糖 - 胰岛素 - 钾（GIK）合剂对心肌缺血/再灌注（MI/R）后心肌细胞死亡（即坏死和凋亡）及心脏功能恢复的影响，并进一步探讨胰岛素在GIK诱导的心脏保护作用中的作用。
雄性Sprague-Dawley大鼠经历30分钟心肌缺血，随后再灌注4小时（用于心脏功能和心肌细胞凋亡研究）或6小时（用于心肌梗死测量）。麻醉的大鼠在再灌注前5分钟开始以4 ml·kg⁻¹·h⁻¹的速度持续输注生理盐水、GIK（葡萄糖：200 g/L，胰岛素：60 U/L，氯化钾：60 mmol/L）、GK或胰岛素，并持续整个4小时的再灌注过程。在整个实验过程中监测动脉血压、心电图和左心室压力。在再灌注结束时测定心肌DNA片段化和心肌梗死情况。
MI/R导致显著的心脏功能障碍和心肌死亡（坏死和明显的DNA梯带形成）。与给予赋形剂处理的大鼠相比，给予GIK处理的大鼠对MI/R损伤表现出保护作用，表现为心肌梗死面积减小[（41.3±8.3）%对赋形剂组的（54.4±10.4）%，P<0.05，n = 10]，DNA片段化明显减少，并且在再灌注结束时心脏收缩/舒张功能恢复改善[左心室舒张末压：（94±6）mmHg对赋形剂组的（86±5）mmHg，P<0.05；+LVdP/dt(max)：（2 940±114）mmHg/s对（2 733±132）mmHg/s，P<0.05；-LVdP/dt(max)：（2 629±156）mmHg/s对（2 463±133）mmHg/s，P<0.05]。胰岛素发挥了与GIK相似的心脏保护作用；而接受GK处理的大鼠对MI/R损伤未表现出任何显著的心脏保护作用。
GIK对缺血后心肌损伤发挥心脏保护作用。胰岛素主要通过其抗凋亡作用，在MI/R中GIK诱导的心肌保护中起关键作用。
