摘要
目的观察心肌缺血预处理对不同病程糖尿病大鼠心肌再灌注性损伤及磷酸化Akt(p-Akt)的影响。方法建立实验性糖尿病大鼠模型,并分别于造模2周和9周后结扎左冠状动脉前降支复制心肌缺血模型。36只SD大鼠随机分为6组(每组6只):非糖尿病缺血预处理组(NDMIP)、非糖尿病缺血再灌注组(NDMIR)、2周糖尿病缺血预处理组(2DMIP)、2周糖尿病缺血再灌注组(2DMIR)、9周糖尿病缺血预处理组(9DMIP)和9周糖尿病缺血再灌注组(9DMIR)。实验结束后检测大鼠肌酸激酶同工酶(CK-MB)、心肌p-Akt的表达,测定心肌梗死范围,并进行心律失常评分。结果NDMIP组CK-MB与2DMIP组比较差异无统计学意义,但明显低于NDMIR组和9DMIP组(P<0.05);2DMIP组CK-MB明显低于9DMIP组(P<0.05)。NDMIP组心律失常评分显著低于ND-MIR组和9DMIP组(P<0.05),但与2DMIP组比较差异无统计学意义(P>0.05);2DMIP组心律失常评分明显低于9DMIP组(P<0.05)。NDMIP组心肌p-Akt的表达明显高于NDMIR组和9DMIP组(P<0.05),与2DMIP组比较差异无统计学意义(P>0.05),而2DMIP明显高于9DMIP组(P<0.05)。NDMIP组梗死区心肌重量/缺血区心肌重量(IS/AAR%)明显低于NDMIR组和9DMIP组(P<0.05),与2DMIP组比较差异无统计学意义(P>0.05);9DMIP组IS/AAR%明显高于2DMIP组(P<0.05)。结论缺血预处理对急性糖尿病大鼠具有保护作用,而对慢性糖尿病大鼠的保护作用不明显,可能与p-Akt通路的激活程度有关。
Objective To evaluate the effect of ischemic preconditioning （IPC） on ischemia reperfusio-injury of myocardium and phosphorylated Akt （p-Akt） during the disease course of diabetes in rats. Methods The rat model of diabetes mellitus was repmdused by streptozocin （40mg/kg, i. v. ）. Myocardial ischemia was then created by temporary ligation of a branch of the left anterior descending （LAD） coronary artery after 2 and 9 weeks, respectively. Thirty six SD rats were randomly divided into six groups （6 each） ： non-diabetic IPC （NDMIP） group, non-diabetic I/R （NDMIR） group, 2 week diabetic IPC （2DMIP） group, 2 week diabetic I/R （2DMIR） group, 9- week diabetic IPC （9DM1P） group and 9 week diabetic I/R （gDMIR） group. Ischemic/reperfusion was induced by temporary occlusion of LAD coronary artery. After the experiment, creatine kinasc-MB （CK MB） isoenzyme and myocardial infarct size were measured, and the expression of p-Akt was detected by Western blotting, the arrhythmia score was then evaluated. Results CK-MB level in NDMIP group was significantly lower than that in NDMIR group and 9DMIP group （P〈0.05）, but no significant difference was found compared with that in 2DMIP group; the CKMB level in 9DMIP group was significantly higher than that in 2DMIP group （P〈0. 05）. The arrhythmia score in NDMIP group was significantly lower than that in NDMIR group and 9DMIP group （P〈0.05）, but no significant difference was found compared with that in 2DMIP group （ P〉0. 05） the arrhythmia score in 9DMIP group was significantly higher than that in 2DMIP group （P〈0. 05）. The expression of tyAkt in NDMIP group was significantly higher than that in NDMIR group and 9DMIP group （P〈0.05）, but no significant difference when compared with that in 2DMIP group （ P〉0. 05） ; the expression of lyAkt in 9DMIP group was significantly lower than that in 2DMIP group （ P〈0. 05）. Myocardial infarct size in NDMIP group was significantly smaller than that in NDMIR group and 9DMIP group （ P〈0.05）, but no significant difference was found when compared with that in 2DMIP group （P〉 0.05） ; the myocardial infarct size in 9DMIP group was larger than that in 2DMIP group. Conclusions IPC can provide significant micro vascular protection against prolonged ischemia/reperfusion in acute diabetic rats, but not in chronic diabetic rats. The attenuation of myo cardial protection by IPC may be associated with a decrease in p-Akt activation.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2009年第4期448-451,共4页
Medical Journal of Chinese People's Liberation Army
关键词
糖尿病
缺血预处理
心肌
蛋白激酶类
diabetes mellitus
ischemic preconditioning, myocardial
protein kinases
