Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
J Cardiol. 2009 Feb;53(1):102-7. doi: 10.1016/j.jjcc.2008.09.012. Epub 2008 Nov 25.
Statins have been reported to be protective against myocardial infarction (MI). Moreover, statin drugs upregulate nitric oxide (NO) in coronary artery independent of lipid-lowering effects. However their precise mechanism for MI-protection is unclear. We investigated the effect of lipophilic statin administration in a normocholesterolemic rabbit MI model.
Nω-nitro-L-arginine methylester (L-NAME, 10 mg/kg) or vehicle alone was intravenously administered 20 min before inducing ischemia, followed by intravenous administration of simvastatin (5 mg/kg) or saline 10 min before ischemia. Rabbits then underwent 30 min of coronary occlusion followed by 48 h of reperfusion. The at-risk and infarct areas were calculated as a percentage of the total left ventricular slice area.
Determination of infarct size revealed that pre-ischemic treatment with simvastatin reduced infarct size (30.5 ± 4%) in comparison to controls (45.0 ± 3%) (P < 0.05). This infarct size-reducing effect of simvastatin could be completely abrogated by pretreatment with L-NAME (42.0 ± 4%).
Pre-ischemic treatment with simvastatin reduces MI size via NO production. Simvastatin could be a useful drug for coronary artery disease patients without dyslipidemia as it has direct protective effects.
他汀类药物已被报道可预防心肌梗死 (MI)。此外，他汀类药物可独立于降脂作用上调冠状动脉中的一氧化氮 (NO)。然而，其预防 MI 的确切机制尚不清楚。我们在正常胆固醇的兔 MI 模型中研究了亲脂性他汀类药物给药的效果。
在诱导缺血前 20 分钟静脉给予 Nω-硝基-L-精氨酸甲酯 (L-NAME，10mg/kg) 或单独的载体，然后在缺血前 10 分钟静脉给予辛伐他汀 (5mg/kg) 或生理盐水。然后，兔子经历 30 分钟的冠状动脉闭塞，随后再进行 48 小时的再灌注。将危险区和梗死区计算为左心室切片总面积的百分比。
梗死面积的测定表明，与对照组 (45.0 ± 3%) 相比，缺血前给予辛伐他汀可减少梗死面积 (30.5 ± 4%) (P < 0.05)。L-NAME 的预处理可完全消除辛伐他汀的这种减少梗死面积的作用 (42.0 ± 4%)。
缺血前给予辛伐他汀可通过产生 NO 来减少 MI 面积。辛伐他汀可能是一种对无血脂异常的冠心病患者有用的药物，因为它具有直接的保护作用。
