乳酸对大鼠急性心肌缺血再灌注损伤后适应的心肌保护作用  

Cardio-Protection of Lactate on Post-Conditioning of Acute Myocardial Ischemia Reperfusion in Rats

作　　者：张国明[1] 王禹[1] 李天德[1] 张大为[1] 刘秀华[2] 李玉珍[2] 

机构地区：[1]中国人民解放军总医院心血管内科,北京市100853 [2]中国人民解放军总医院病理研究室,北京市100853

出　　处：《中国循环杂志》2010年第1期34-37,共4页Chinese Circulation Journal

基　　金：国家自然科学基金(No.30740080)

摘　　要：目的:在大鼠急性心肌缺血再灌注中,探讨乳酸延长局部组织酸中毒能否模拟后适应发挥有效的心肌保护作用。方法:72只SD大鼠随机分为假手术组、再灌注损伤组、后适应组和乳酸组,每组18只。测定再灌注10min后右心房血浆pH值,并在不同时间点处死大鼠,分别测定心肌酶活力、心肌丙二醛含量、超氧化物歧化酶活性、心肌组织线粒体吸光度,磷酸化的细胞外信号调节蛋白激酶、线粒体调控因子Bcl-2和Bax的表达,以及细胞凋亡和心肌梗死面积。结果:再灌注10min后乳酸组与后适应组右心房血浆pH值相似(P>0.05)。再灌注1h后乳酸组和后适应组同再灌注损伤组相比均显著抑制了线粒体吸光度的降低(P<0.05),但再灌注6h后乳酸组抑制作用明显减弱(P>0.05)。乳酸组和再灌注损伤组相比未改变心肌组织丙二醛含量和超氧化物歧化酶活性(P>0.05)。磷酸化的细胞外信号调节蛋白激酶、Bcl-2和Bax的表达上乳酸组虽优于再灌注损伤组(P<0.05),但同后适应组相比差异仍有统计学意义(P<0.05)。另乳酸组可不同程度降低心肌酶活力、凋亡指数和心肌梗死面积,但凋亡指数仍显著高于后适应组(P<0.05)。结论:乳酸可以部分模拟后适应带来的保护效应,局部酸中毒的短暂延长可能只是后适应最上游触发因子之一。Objective ：To test the hypotheses of lactate mimicking cardio-protection of post-conditioning by prolonging local acidosis of acute myocardial ischemia reperfusion in rats. Methods ： Seventy two rats were randomized into 4 groups ： Sham operation group, Reperfusion/injury （ R/I group）, Post-conditioning （Post group） ,the animats were treated with 4 cycles of 20/20 s of reperfusion/re-occlusion, and Lactate group, the animats were treated with micro-injection of lactate at ischemic myocardium. There were 18 rats in each group. Blood was taken from right atrium 10 minutes after reperfusion to measure pH. All rats were executed at different time points to examine the contents of malonic dialdehyde （MDA）, superoride dismutase （SOD）, and the absorption of mitochondria in myocardium. Western blot analysis was used to analyze the expression of phosphorylated ERK1/2 （P-ERK）, Bel-2 and Bax~ Myocardial apoptosis and infarct size were also determined. Results ： Blood pH was similar in Lactate group and Post group （ P 〉 0. 05 ） 10 minutes after the reperfusion. Compared with R/I group, the myocardial absorption in Lactate group and Post group were both decreased 1 h after the reperfusion （P 〈 0. 05）, and this phenomenon was attenuated 6h after reperfusion （P 〉 0, 05 ）. The levels of MDA and SOD in myocardium were similar in Lactate group and R/I group （ P 〉 0. 05 ）. The expressions of P-ERK, Bcl-2 and Bax in Lactate group were higher than that in R/I group （P 〈 0.05 ）, but lower than that in Post group （P 〈 0.05 ）. Myocardial enzyme activity, apoptotic index and infarct size in Lactate group were decreased at different degree, but apoptotic index was still higher than that in Post group （P 〈 0. 05）. Conclusion ： Lactate could partly mimic the cardio-protection of post-conditioning, and brief prolonged local acidosis in ischemic myocardium might be one of trigger factors in the complex mechanism of post-conditioning.

关 键 词：后适应 再灌注损伤 乳酸 酸中毒 线粒体通透性转换孔 

分 类 号：R54[医药卫生—心血管疾病]