胰岛素在葡萄糖-胰岛素-钾对急性心肌缺血再灌注家兔抗凋亡作用中的角色。

Role of insulin in the anti-apoptotic effect of glucose-insulin-potassium in rabbits with acute myocardial ischemia and reperfusion.

作者信息

Zhang H F, Fan Q, Qian X X, Lopez B L, Christopher T A, Ma X L, Gao F

机构信息

Department of Physiology, The Fourth Military Medical University, Xi'an 710032, China.

出版信息

Apoptosis. 2004 Nov;9(6):777-83. doi: 10.1023/B:APPT.0000045796.58715.82.

DOI:10.1023/B:APPT.0000045796.58715.82

PMID:15505420

Abstract

OBJECTIVE

To study the effects of glucose-insulin-potassium (GIK) cocktail on cardiac myocyte apoptosis and cardiac functional recovery following myocardial ischemia/reperfusion (MI/R), and to further determine the role of insulin in the GIK-induced cardioprotective effect in vivo .

METHODS

Forty eight male rabbits were subjected to 40 min MI followed by R for 3 h and were randomly received one of the following treatments: saline, GIK (glucose: 150 g/L, insulin: 60 U/L and KCl: 80 mmol/L), or insulin (n = 16 in each group) at 1 ml x kg(-1) x h(-1), beginning 30 min before MI and continuing throughout the 3 h-reperfusion. Blood glucose, electrolytes, arterial blood pressure and left ventricular pressure (LVP) were monitored throughout the experiment. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activity were measured spectrophotometrically. Myocardial infarction and myocardial apoptosis (both DNA laddering and TUNEL analysis) were determined in a blinded manner.

RESULTS

MI/R caused significant cardiac dysfunction and myocardial apoptosis (both strong DNA ladder formation and TUNEL-positive staining). Compared with vehicle, GIK-treated rabbits showed protection against MI/R as evidenced by reduced myocardial infarction (19.7% +/- 2.6% vs . 26.8% +/- 3.3% of vehicle, n = 10, P < 0.05), marked decrease in DNA fragmentation and apoptotic index (11.0% +/- 2.1% vs . 20.1% +/- 3.1% of vehicle, n = 6, P < 0.01), significant decrease of plasma CK and LDH and improved recovery of cardiac systolic/diastolic function at the end of R. Treatment with insulin alone decreased blood glucose significantly but still exerted cardioprotective effects comparable with that of GIK.

CONCLUSIONS

GIK exerts cardioprotective effects against postischemic myocardial injury and improves cardiac functional recovery in vivo . Insulin, mainly through the anti-apoptotic effect, plays a key role in the GIK-elicited myocardial protection in MI/R.

摘要

目的

研究葡萄糖-胰岛素-钾（GIK）合剂对心肌缺血/再灌注（MI/R）后心肌细胞凋亡及心脏功能恢复的影响，并进一步确定胰岛素在GIK诱导的体内心脏保护作用中的作用。

方法

48只雄性兔接受40分钟的MI，随后再灌注3小时，并随机接受以下治疗之一：生理盐水、GIK（葡萄糖：150 g/L，胰岛素：60 U/L，氯化钾：80 mmol/L）或胰岛素（每组n = 16），剂量为1 ml·kg⁻¹·h⁻¹，在MI前30分钟开始给药，并在整个3小时再灌注期间持续给药。在整个实验过程中监测血糖、电解质、动脉血压和左心室压力（LVP）。采用分光光度法测定血浆肌酸激酶（CK）和乳酸脱氢酶（LDH）活性。以盲法测定心肌梗死和心肌凋亡（DNA梯状条带和TUNEL分析）。

结果

MI/R导致明显的心脏功能障碍和心肌凋亡（DNA梯状条带形成和TUNEL阳性染色均明显）。与对照组相比，GIK治疗的兔表现出对MI/R的保护作用，表现为心肌梗死面积减小（19.7%±2.6%对对照组的26.8%±3.3%，n = 10，P < 0.05），DNA片段化和凋亡指数明显降低（11.0%±2.1%对对照组的20.1%±3.1%，n = 6，P < 0.01），血浆CK和LDH明显降低，再灌注结束时心脏收缩/舒张功能恢复改善。单独使用胰岛素治疗可显著降低血糖，但仍发挥与GIK相当的心脏保护作用。