Low invasive therapy with gratnilotyte colony stimulating factor in patients with coronary artery dicease

1)急性心肌梗死患者，经左心室图分析，心肌梗死后1个月，皮下注射剂量为2- 5mg/kg的G-CSF可显著改善射血分数（Suzuki K, et al. Circ J 2006）。2)缺血前10分钟，兔冠状动脉闭塞30分钟，再灌注48小时普伐他汀（1或5mg/kg）或生理盐水。再灌注前10分钟给予普伐他汀（5mg/kg）。在普伐他汀注射前10分钟静脉注射L-NAME （10mg/kg）、chelerythrine （5mg/kg）或5-HD （5mg/kg）。测定梗死面积。测定大鼠心肌间质2,5 - dhba、NOx水平及心肌双氢乙啶染色强度。与对照组（45±3%）相比，普伐他汀缺血前治疗可减少梗死面积（分别为34±5%和24±4%，1和5mg/kg），但再灌注前治疗不能减少梗死面积（42.1±3.7%）。L-NAME（42.6±4%）、chelerythrine（50.9±3%）和5-HD（52.7±2%）分别阻断了这一作用。缺血前普伐他汀处理增加心肌NOx水平，减弱再灌注时2,5- dhba水平和双氢乙酯染色强度。车车草碱消除了普伐他汀引起的氮氧化物水平的增加。普伐他汀缺血前治疗通过蛋白激酶c依赖性一氧化氮生成、减少羟基自由基和超氧化物以及打开线粒体KATP通道来减小心肌梗死面积。

1) In patients with acute myocardial infarction, subcutaneous treatment with G-CSF at a dose of 2-5 mg/kg significantly improved ejection fraction at 1 months after myocardial infarction assacsed by left ventriculogram (Suzuki K, et. al. Circ J 2006)2) Rabbits underwent 30 min of coronary occlusion followed by 48 hours of reperfusion Pravastatin (1 or 5mg/kg) or saline was intravenously administered 10 min before ischemia. Pravastatin (5mg/kg) was also administered 10 min before reperfusion. L-NAME (10mg/kg), chelerythrine (5mg/kg) or 5-HD (5mg/kg) was i.v. administered 10 min before pravastatin injection. The infarct size was determined. The myocardial interstitial levels of 2, 5-DHBA and NOx, and the intensity of myocardial dihydroethidium staining were obtained. Pre-ischemic treatment with pravastatin reduced the infarct size (34±5% and 24±4%, 1 and 5mg/kg, respectively) but not pre-reperfusion treatment (42.1±3.7%) compared with the control (45±3%). This effect was blocked by L-NAME (42.6±4%), chelerythrine (50.9±3%) and 5-HD (52.7±2%), respectively. Pre-ischemic treatment with pravastatin increased myocardial NOx levels and attenuated the 2,5-DHBA levels and the intensity of dihydroethidium staining during reperfusion. Chelerythrine abolished the increase in NOx levels by pravastatin. Pre-ischemic treatment with pravastatin reduces the myocardial infarct size via protein kinase C-dependent nitric oxide production, decreasing hydroxyl radicals and superoxide, and opening the mitochondrial KATP channels.