摘要
目的:建立离体大鼠心肌缺血/再灌注损伤模型,观察缺血后处理对大鼠心肌线粒体功能的影响,并探讨线粒体ATP敏感性钾通道(mitoKATP)在缺血后处理心肌保护中的作用。方法:采用Langendorff装置建立离体大鼠心肌缺血/再灌注损伤模型。将SD大鼠随机分为对照组(C)、模型组(M)、缺血后处理组(IPO)、5-羟癸酸拮抗缺血后处理组(5-HD+IPO),每组8只。各组均先灌注平衡20 min,C组:续灌70 min;M组:缺血前灌注4℃St.Thomas停跳液(10 mL/kg),全心缺血40 min,复灌30 min;IPO组:全心缺血40 min,复灌前先开放10 s,缺血10 s,反复6次,时间为2 min,复灌28 min;5-HD+IPO组:缺血后处理前给予含5-羟癸酸(100μmol/L)的K-H液灌注5 min,余同IPO组,复灌23 min。观察各组平衡末与再灌注末心肌线粒体膜电位、氧自由基及呼吸功能的变化。结果:(1)各组再灌注末心肌线粒体膜电位较平衡末显著降低,而C组显著高于其它3组,IPO组明显高于5-HD+IPO与M组,5-HD+IPO组高于M组。(2)各组再灌注末与平衡末比较,心肌线粒体氧自由基含量显著升高,其中M组显著高于其它3组,5-HD+IPO组高于IPO及C组,IPO组高于C组。(3)各组再灌注末较平衡末线粒体呼吸功能明显受损,且C组优于其它3组,IPO组优于5-HD+IPO与M组,5-HD+IPO组优于M组。结论:(1)缺血后处理通过维护线粒体膜电位稳定、减少线粒体氧自由基的产生、保护线粒体呼吸链及功能,减轻心肌的再灌注损伤。(2)5-HD不能完全阻断缺血后处理的心肌保护作用。(3)缺血后处理的心肌保护效应可通过激活心肌mitoKATP实现,同时还有其它因素参与了缺血后处理的心肌保护。
AIM ： To investigate the protective effect of ischemic post - conditioning on isolated rat myocardial mitochondrial function during ischemia/reperfusion, and to study the role of mitoehondrial ATP - sensitive potassium chan- nel（ mitoKArr ） in myocardial protection. METHODS： Sprague - Dawley male rats were randomized into 4 groups（ n = 8 in each group） ： control group（C）, model group（M）, ischemie post -conditioning group（IPO） and 5 -hydroxydecanoate plus IPO group（5 - HD ＋ IPO）. The hearts isolated from the SD rats were mounted on a Langendorff apparatus and started with a 20 - minute perfusion for equilibration. In C group, the hearts went on perfusion for another 70 min after equilibra- tion. In M group, 4 ℃ St. Thomas cardioplegic solution was administered prior to isebemia, followed by iscbemia for 40 - minute, and reperfusion for another 30 min. In IPO group, the hearts underwent 40 - minute global ischemia after equili- bration, then perfusion for 10 s and iscbemia for another 10 s. The procedure was repeated 6 times before 28 - minute reperfusion. In 5 - HD ＋ IPO group, the hearts were perfused with 5 - HD（ 100 μmol/L in K - H solution） and treated as that in IPO group, then reperfusion for 23 min. The reactive oxygen species （ ROS）, mitoehondrial membrane potential （MMP） and respiratory function of myocardial mitoehondria were measured at the ends of equilibration and reperfusion. RESULTS ： （ 1 ） Compared with the data collected at the end of equilibrium, the MMP was obviously decreased at the end of reperfusion in all groups, The highest in C group. MMP in 5 - HD ＋ IPO group was markedly higher than that in IPO group arid M group. MMP in IPO group was higher than that in M group. （2） In contrast to that at the end of equilibrium, ROS was obviously increased at the end of reperfusion in all groups. However, ROS was observably higher in M group than that in the other 3 groups, and ROS in 5 - HD ＋ IPO group was markedly higher than that in IPO group and C group. ROS in IPO group was higher than that in C group. （3） The respiratory function of mitochondria was obviously injured at the end of reperfusion in all groups. The arrangement of the mitochondrial respiratory function from the best to the worse was C group 〉 IPO group 〉 5 - HD ＋ IPO group 〉 M group. CONCLUSION： Ischemic post - conditioning attenuates myocardial reperfusion injury by maintaining the stability of MMP, decreasing the generation of ROS and preserving the respiratory chain function of mitochondria. The mitoKATP antagonist 5 - HD can not completely block the myocardial protective effect of ischemic post - conditioning. Myocardial protective effect of ischemic post - conditioning may achieve by activating mi- toKATP, meanwhile the other factors may also take part in the myocardial orotective processes.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2011年第2期229-233,共5页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.30740044)
贵州省科技基金资助项目[No.(2007)2121号]
关键词
线粒体功能
缺血后处理
再灌注损伤
心肌
Mitochondrial function
Ischemic postconditioning
Reperfusion injury
Myocardium
