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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%)50min,再灌注4h。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(19·2ml/min±2·2ml/minvs14·6ml/min±1·8ml/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。
Objective To observe the effects of insulin on cardiac function, coronary blood flow, coronary diastolic function and coronary artery endothelial cell apoptosis in acute myocardial ischemia / reperfusion (MI / R) dogs. Methods The canine MI / R model was established. Myocardial ischemia (left anterior descending branch blood flow reduced by 80%) for 50 min and reperfusion for 4 h. The rats were randomly divided into saline, glucose-insulin-potassium solution (GIK), glucose-potassium solution (GK) and sham operation group. The coronary blood flow and hemodynamic parameters were measured; coronary vessels were isolated after reperfusion The coronary diastolic function was observed in vitro by perfusion and the content of NO in perfusate was measured. The apoptosis of coronary artery endothelial cells was detected by in situ end labeling. Results Compared with saline group, the anterior descending coronary artery blood flow (CBFLAD) increased in the GIK group (19.2 ml / min ± 2.2 ml / min vs 14.6 ml / min ± 1.8 ml / min, P <0.05) And improve left ventricular systolic and diastolic function after reperfusion, while the GK group did not. Compared with the sham-operation group, MI / R saline group had obvious coronary diastolic dysfunction, decreased NO release and apoptosis of coronary vascular endothelial cells. GIK group could effectively protect coronary diastolic function (P <0.01) and increase NO release (P <0.01). Insulin also significantly inhibited MI / R induced apoptosis of vascular endothelial cells (12% ± 4%) and saline group (45% ± 7%, P <0.01). Conclusions Administration of insulin during reperfusion can significantly reduce the coronary artery injury caused by MI / R, increase coronary blood flow, effectively promote the recovery of cardiac function and protect the ischemic heart. The role of insulin and promote endothelial NO production, inhibition of MI / R coronary artery endothelial cell apoptosis.