二氮嗪对低温保存诱导的心肌线粒体氧自由基的清除作用  

Elimination of Oxygen Free Radicals in Rat Myocardial Mitochondria by Diazoxide During Hypothermic Preservation

作　　者：严志焜[1] 郑鸣之[2] 胡志斌[1] 蒋建平[2] 张晓明[3] 朱立[3] 陈莹莹[3] 沈岳良[3] 

机构地区：[1]浙江省人民医院,杭州310014 [2]浙江医学高等专科学校,杭州310053 [3]浙江大学医学院,杭州310058

出　　处：《医学研究杂志》2008年第11期45-49,共5页Journal of Medical Research

基　　金：浙江省科技厅重点科研项目(2005C23033);国家自然科学基金项目(30470635);浙江省科技厅一般科研项目(2007C33026);浙江医学高等专科学校科技计划项目(2006XZ04)资助

摘　　要：目的观察二氮嗪(diazoxide,DE)对不同时程低温保存诱导产生的大鼠心肌细胞线粒体内氧自由基的清除作用。方法根据不同的低温保存时程,SD大鼠随机分9组,每组8只。利用Langendorff离体鼠心灌注法停搏大鼠心脏,然后在4℃单纯Celsior保存液或加入DE(30μmol/L)的Celsior保存液中分别保存0h、3h、6h、9h或12h后,检测心肌细胞线粒体内超氧化物歧化酶(superoxide dismutase,SOD)活性和丙二醛(maleic dialdehyde,MDA)含量的变化。且同步观察电镜下心肌超微结构的变化。结果①与对照组比较,随着冷保存时间的延长,心肌细胞线粒体内SOD活性随之降低,MDA含量随之升高,电镜结果显示心肌细胞线粒体超微结构随之破坏加剧;②与相应低温保存时程的单纯celsior液组比较,在保存液中加入DE后,上述各项指标均有明显改善,且以冷保存6h和9h后最为显著。结论DE在大鼠心脏长时程低温保存期间可通过直接清除自由基及提高线粒体SOD活力而减轻由长时程低温保存导致的心肌细胞线粒体的损伤。Objective To observe the elimination of oxygen free radicals in rat myocardium mitochondria by diazoxide （DE） during different duration of hypothermic preservation. Methods The Langendorff model of isolated rat heart was used. After stored in 4℃ Celsior solution or Celsior solution containing 30 μmol/L of DE for different duration （0,3,6,9 or 12h） , the activity of the superoxide dismutase （SOD） and the content of maleic dialdehydc （MDA） in heart mitochondrial were measured. The myocardial mitochondria uhrastructure was also evaluated. Results （ 1 ） After hypothermic preservation,the activity of SOD was decreased,the content of MDA was increased. The uhrastructure of myocardium mitochondria was also destrored in preserved rat hearts in a time - dependent manner. （2） Compared with the corresponding Cclsior solution hypothermic preservation groups, DE significantly improved the above indexes （SOD, MDA and myocardial mitoehondria uitrastructure）. Conclusion Diazoxide can protect rat myocardial mitochondria from long - term hypothermie preservation injury by direct elimination of oxygen free radials and enhancement of the activity of SOD.

关 键 词：二氮嗪 心 冷保存 超氧化物岐化酶 丙二醛 

分 类 号：R542.2[医药卫生—心血管疾病] R657.3[医药卫生—内科学]