摘要
目的:探讨线粒体ATP敏感性钾通道开放剂二氮嗪(DE)对离体大鼠心脏冷保存效果的影响及作用机制。方法:SD大鼠随机分成对照组、DE组、DE+5-HD组。利用Langendorff离体鼠心灌注法,各组心脏在4℃条件下分别保存3h和8h后,复灌60min,观察各组大鼠血流动力学的恢复情况、冠脉流出液中心肌酶漏出量、心肌水含量的变化及心肌超微结构改变。结果:在Celsior心麻痹液中添加30μmol/L的DE后,能明显改善冷保存3h心脏的左心室发展压力的恢复,降低心肌酶(LDH、CK)在某些复灌时间点上的漏出,但对保存后左心室舒张末期压力的抬高和冠脉流量的恢复及心肌水肿程度无明显作用;而相同浓度的DE添加到Celsior心麻痹液中,可明显降低冷保存8h心脏左心室舒张末期压力的抬高,改善左心室发展压力和冠脉流量的恢复,降低心肌酶(LDH、CK、GOT)的漏出,缓解心肌水肿,对心肌的超微结构也有较好的保护作用,其中30和45μmol/LDE组对冷保存8h心脏的保护作用优于15μmol/LDE组,而30及45μmol/LDE组之间并无显著性差异。DE的上述作用可被线粒体ATP敏感性钾通道的特异性阻断剂5-HD所取消。结论:DE可通过激活线粒体ATP敏感性钾通道显著改善离体大鼠心脏冷保存效果。
Objective： To investigate whether the mitochondrial ATP-sensitive potassium channel （mitoKATP）opener diazoxide as an additive to cardioplegia solution could enhance myocardial protection during hypothermic preservation of the rat heart. Methods： The Langendorff model of isolated rat heart was used. After equilibrium, the hearts were stored in Celsior cardioplegia solution at 4 C with or without supplement of diazoxide for 3 or 8 h followed by 60 minutes reperfusion. The recovery of cardiac contractile function,myocardial enzyme leakage in the coronary effluent, and myocardial water content were determined. The myocardial ultrastructure was also observed. Results： （1） Treatment of diazoxide improved the recovery of left ventricular developed pressure and decreased the leakage of myocardial enzymes,lactate dehydrogenase （LDH） and creatine kinase （CK）,at the 2nd and 4th minute of reperfusion of rat heart after hypothermic preservation for 3 h. （2） After hypothermic preservation for 8 h,diazoxide improved the recovery of left ventricular developed pressure and decreased the leakage of myocardial enzymes （LDH,CK and glutamic oxalic transaminase） during reperfusion. Moreover, left ventricular end-diastolic pressure was significantly lower in diazoxide-treated hearts than that of hearts in Celsior solution. （3） Diazoxide significantly decreased the water content of myocardium and increased coronary flow of the hearts compared with those in control after hypothermic preservation for 8 h. （4） Impairment of myocardial ultrastructure after 8 h hypothermic preservation was alleviated in hearts treated with 30 mol/L diazoxide. （5） The cardiac effects of 30 mol/L diazoxide were attenuated by a mitoKAP blocker 5-hydroxydecanoate （100 μmol/L） . Conclusion： Diazoxide as a supplementation in cardioplegia solution could enhance myocardial protection during hypothermic heart preservation via opening of mitochondrial KATP channel.
出处
《浙江大学学报（医学版）》
CAS
CSCD
2005年第4期331-338,共8页
Journal of Zhejiang University(Medical Sciences)
基金
国家自然科学基金资助项目(30470635)
