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

玻璃体集落刺激因子低创治疗冠状动脉疾病

基本信息

批准号：
18590765
负责人：
MINATOGUCHI Shinya
金额：
$ 2.49万
依托单位：
Gifu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

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.

1)在急性心肌梗死患者中，通过左心室造影片评估，以2-5 mg/kg剂量皮下注射G-CSF可显着改善心肌梗死后1个月的射血分数（Suzuki K，et. 2）兔经历30分钟的冠状动脉闭塞，随后再灌注48小时，在缺血前10分钟静脉内施用普伐他汀（1或5 mg/kg）或盐水。再灌注前10 min给予普伐他汀5 mg/kg。注射普伐他汀前10分钟静脉注射L-NAME（10 mg/kg）、白屈菜红碱（5 mg/kg）或5-HD（5 mg/kg）。测定梗死面积。测定心肌间质中2，5-DHBA和NOx的含量及心肌二氢乙锭染色强度。与对照组（45±3%）相比，缺血前普伐他汀治疗（1和5 mg/kg）分别减少了梗死面积（34±5%和24± 4%），但再灌注前治疗（42.1±3.7%）没有减少。L-NAME、白屈菜红碱和5-HD可分别阻断上述作用（42.6±4%、50.9±3%和52.7±2%）。缺血前用普伐他汀治疗增加心肌NOx水平，并减弱再灌注期间2，5-DHBA水平和二氢乙锭染色强度。白屈菜红碱消除了普伐他汀引起的NOx水平升高。缺血前用普伐他汀治疗通过蛋白激酶C依赖的一氧化氮产生、减少羟基自由基和超氧化物以及开放线粒体KATP通道来减少心肌梗死面积。