Pravastatin reduces myocardial infarct size via increasing protein kinase C-dependent nitric oxide, decreasing oxyradicals and opening the mitochondrial adenosine triphosphate-sensitive potassium channels in rabbits
Pravastatin reduces myocardial infarct size via increasing protein kinase C-dependent nitric oxide, decreasing oxyradicals and opening the mitochondrial adenosine triphosphate-sensitive potassium channels in rabbits
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DOI：
10.1253/circj.71.1622
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发表时间：
2007-10-01
影响因子：
3.3
通讯作者：
Fujiwara, Hisayoshi
中科院分区：
文献类型：
--
作者：
Bao, Narentuoya;Minatoguchi, Shinya;Fujiwara, Hisayoshi
背景据报道他汀类药物对心肌梗死有保护作用，但确切的机制尚不清楚。方法和结果兔冠状动脉闭塞30min，再灌注48h。缺血前10min静脉注射普伐他汀(1 mg/kg或5 mg/kg)或生理盐水。再灌流前10min给予普伐他汀(5 mg/kg)。普伐他汀注射前10min静脉注射N-奥米伽-硝基-L-精氨酸甲酯(L-NAME，10 mg/kg)、白屈菜红碱(5 mg/kg)或5-羟基癸酸钠(5-HD，5 mg/kg)。测定心肌梗死面积。测定心肌间质中2，5-二羟基苯甲酸(DHBA)和一氧化氮(NOx)水平及心肌二氢乙锭染色强度。与对照组(45+/-3%)相比，缺血前应用普伐他汀可缩小心肌梗死面积(分别为34+/-5%和24+/-4%、1 mg/kg和5 mg/kg)，但不能缩小再灌注前(42.1+/-3.7%)的心肌梗死面积。此作用可被L-NAME(42.6+/-4%)、白屈菜红碱(50.9+/-3%)和5-HD(52.7+/-2%)阻断。缺血前应用普伐他汀可增加心肌NOx水平，降低再灌流期间2，5-DHBA水平和二氢乙锭染色强度。结论普伐他汀缺血前应用普伐他汀可减少心肌梗死面积，其机制可能是通过产生依赖蛋白激酶C的一氧化氮，减少羟基自由基和超氧阴离子自由基，开放线粒体三磷酸腺苷敏感性钾通道来实现的。
Background Statins reportedly protect against myocardial infarction, but the precise mechanism is unclear.Methods and Results Rabbits underwent 30 min of coronary occlusion followed by 48 h of reperfusion. Pravastatin (I or 5 mg/kg) or saline was intravenously administered 10 min before ischemia. Pravastatin (5 mg/kg) was also administered 10min before reperfusion. N-omega-nitro-L-arginine methylester (L-NAME, 10mg/kg), chelerythrine (5mg/kg) or 5-hydroxydecanoic acid sodium salt (5-HD, 5mg/kg) was intravenously administered 10min before pravastatin injection. The infarct size was determined. The myocardial interstitial levels of 2,5dihydroxybenzoic acid (DHBA) and nitrogen oxide (NOx), and the intensity of myocardial dihydroethidium staining were measured. Pre-ischemic treatment with pravastatin reduced the infarct size (34 +/- 5% and 24 +/- 4%, 1 and 5 mg/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%). Pre-ischemic treatment with pravastatin increased myocardial NOx levels, and attenuated both the 2,5-DHBA level and the intensity of dihydroethidium staining during reperfusion. Chelerythrine abolished the increase in NOx levels by pravastatin.Conclusion 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 adenosine triphosphate-sensitive potassium channels.