摘要
目的研究线粒体三磷酸腺苷敏感性钾通道(mitoKATP)、一氧化氮合酶(NOS)在四氢生物蝶呤(BH4)减轻心肌缺血再灌注损伤(MIRI)中的作用。方法将64只成年大白兔随机分成4组,建立Langendorff模型灌注其离体心脏,加入不同成分的K-H液灌流、停跳、复灌,观察冠脉流量(CF),测定冠脉流出液肌酸激酶(CK)的含量以及心室肌NO含量。结果用含BH4的K-H液灌注的组Ⅱ再灌注后的CF、心肌NO含量增加,冠脉流出液中CK的含量降低。使用含NOS抑制剂L-NAME或mitoKATP抑制剂5-HD预处理,使CF降低,冠脉流出液中CK的含量升高,同时L-NAME预处理后的心肌组织NO含量较其他组下降,各差异均有统计学意义(P<0.05)。结论外源性BH4具有抗MIRI的作用,而mi-toKATP、NOS参与了这种作用。提高NOS的活性,促进内源性NO的产生,mitoKATP的开放是保护作用的可能机制。
Objective To study the effect of tetrabydrobiopterin （ BH4 ）, 5-hydroxydecanoate （ 5-HD ） and Nω-nitro-L-arginine methyl ester（L-NAME） on langendorff rabbit heart model. Methods Sixty-four mature rabbits were randomly divided into four groups. The hearts in vitro removed to Langendoff equipment, then perfused with different buffer solution base on the Krebs-Henseleit buffer（KHB） for 30 min. Then cardiac arrest was induced for 30 min followed by 60 min reperfusion. Coronary flow（CF） was recorded. Coronary effluent solution was collected for CK measurion. The dynamic change of myocardial NO content was measured. Results By the treatment with BH4, CF was significantly increased, and CK was decreased than other groups after reperfusion（ P 〈 0. 05 ）. By the pre-treatment with L-NAME, a specific inhibitor of nitric oxide synthase, or 5-HD, a specific inhibitor of mitochondrial ATP-sensitive potassium channel（ mitoKATP channel） , CF was significantly decreased, and CK was increased than other groups after reperfusion. By the pre-treatment with L-NAME, NO levels were decreased than other groups （ P 〈 0.05 ）. Conclusion These findings suggest that BH4 has a eardioprotective effect against myocardial ischemia-reperfusion injury（MIRI） in vitro. The protective effect of BH4 appeared to be involved in the opening of mitoKATP channels and the activating NOS then increase the NO production.
出处
《中国实用医药》
2009年第1期13-14,共2页
China Practical Medicine
