胰岛素对急性心肌缺血再灌注犬心脏及冠状动脉动能的影响

目的 观察胰岛素对急性心肌缺血/再灌注(MI/R)犬心脏功能、冠脉血流量、冠状动脉舒张功能及冠脉血管内皮细胞凋亡的影响.方法 制备犬MI/R模型,心肌定量缺血(左前降支血流量降低80%)50 min,再灌注4 h.随机分为生理盐水、葡萄糖-胰岛素-钾液(GIK)、葡萄糖-钾液(GK)和假手术组,检测冠脉血流量及血流动力学指标;再灌注结束后分离冠脉血管,行离体血管灌流观察冠脉舒张功能,同时测定灌流液中的NO含量,并采用原位末端标记法检测冠脉血管内皮细胞凋亡.结果 GIK组比生理盐水组左前降支冠脉血流量(CBFLAD)有所增加(19.2 ml/min±2.2 ml/minvs 14.6 ml/min±1.8 ml/min,P＜0.05),并改善再灌注后左室收缩及舒张功能,而GK组无上述作用.与假手术组相比,MI/R生理盐水组有明显的冠脉舒张功能障碍、NO释放量下降和冠脉血管内皮细胞大量凋亡.GIK组可有效保护冠脉舒张功能(P＜0.01),增加NO的释放量(P＜0.01).同时发现胰岛素明显抑制MI/R引起的冠脉血管内皮细胞凋亡(12%±4%),生理盐水组(45%±7%,P＜0.01).结论 再灌注时给予胰岛素可明显减少MI/R导致的冠状动脉损伤,增加冠脉血流量,有效促进心脏功能恢复,保护缺血心脏.该作用与胰岛素促进冠脉内皮NO生成,抑制MI/R冠脉血管内皮细胞凋亡有关.

Effects of insulin on cardiac function and coronary circulation in acute myocardial ischemia and reperfusion experiment with dogs

OBJECTIVE: To study the effect of insulin on cardiac functional recovery, coronary blood flow (CBF), coronary arterial function and coronary vascular endothelial cell apoptosis following acute myocardial ischemia/reperfusion (MI/R). METHODS: In adult dogs, the left anterior descending coronary artery (LAD) was partially occluded (80% reduction in its blood flow) for 50 min and reperfused for 4 h. Vehicle (0.9% NaCl), GIK (glucose: 250 gxL(-1), insulin: 60 UxL(-1), potassium: 80 mmolxL(-1)), or GK (glucose: 250 gxL(-1), potassium: 80 mmolxL(-1)) were intravenously infused (2 mlxkg(-1)xh(-1)) 5 min before reperfusion, and CBF and left ventricular pressure were monitored. At the end of 4 h reperfusion period, coronary arteries were isolated, and the coronary vascular dysfunction, nitric oxide (NO) production and endothelial apoptosis were determined. RESULTS: During reperfusion, compared with the vehicle, GIK increased CBFLAD (19.2 ml/min +/- 2.2 ml/min) vs (14.6 ml/min +/- 1.8 ml/min) of vehicle at the end of reperfusion, P < 0.05, improved recovery of LVSP and +/- LVdP/dtmax. In vivo ischemia/reperfusion caused significant coronary vascular endothelial dysfunction as evidenced by reduced endothelium dependent vasorelaxation, decreased total NO production, and endothelial cell apoptosis as determined by TUNEL staining. Reperfusion with GIK, but not GK, markedly improved the endothelium-dependent vasorelaxation (80.3% +/- 3.8%) vs. vehicle (28.1% +/- 2.3%, P < 0.01) of coronary artery in response to ACh. GIK significantly increased total NO production (17.19 micromol/L +/- 2.18 micromol/L) versus vehicle (4.74 micromol/L +/- 2.01 micromol/L, P < 0.01) and inhibited apoptosis in coronary arterial endothelial cell (12% +/- 4%) vs vehicle (45% +/- 7%, P < 0.01). GK failed to show any significant vasculoprotection against MI/R-induced coronary vascular injury. CONCLUSION: These results demonstrate that insulin exerts cardioprotective effect by increasing CBF, reducing coronary artery injury and improving cardiac functional recovery during reperfusion, which may be partly attributable to the coronary vasculoprotective effect of insulin. The insulin-induced, NO-mediated anti-endothelial apoptotic effect may play a critical role in the insulin-induced coronary artery protective effect in MI/R.