MLA预处理对老年大鼠心肌缺血/再灌注损伤的影响及NF-κB在其中的作用  

Role of NF-κB in the late phase of monophosphoryl lipid A preconditioning on ischemia/reperfusion injury in old rats heart

作　　者：程芳洲[1] 马业新[1] 余细球[1] 鲍翠玉[1] 吴基良[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院心内科,湖北武汉430030

出　　处：《现代医学》2005年第2期74-77,共4页Modern Medical Journal

基　　金：湖北省教育厅科研基金资助项目 (2 0 0 4Q0 0 2 )。

摘　　要：目的　探讨单磷酰脂A(monophosphoryllipidA ,MLA)预处理2 4h对老年大鼠心肌缺血/再灌注损伤的影响及核转录因子 κB(NF κB)在其中的作用。方法　建立老年大鼠心肌缺血/再灌注损伤模型。3 6只大鼠随机分为3组,分别行单纯缺血/再灌注及应用MLA、NF κB的特异性抑制剂DDTC加MLA预处理心脏2 4h后,对心脏进行较长时间缺血/再灌注,检测心肌梗死范围、乳酸脱氢酶(LDH)释放及心肌细胞凋亡率。另外3 0只大鼠随机分为5组,检测MLA预处理0、15、3 0、60min及DDTC加MLA预处理后3 0min时NF κB活性。结果　MLA预处理可减小心肌梗死范围(P <0 .0 5 ) ,降低血浆LDH活性(P <0 .0 5 ) ,减少心肌细胞凋亡率(P <0 .0 1)。预处理使NF κB呈时间依赖性激活,预处理前NF κB活性低,预处理15min开始升高、3 0min达到高峰、60min开始下降。而应用NF κB抑制剂DDTC可完全阻断NF κB复合物活性的增加,也完全消除预处理的保护作用。结论　MLA预处理2 4h对老年大鼠心肌再次缺血/再灌注损伤有保护作用。NF κB参与老年大鼠心肌预处理后的延迟保护作用,MLA预处理后NF κB快速的核转移并激活可能是药物预处理延迟保护作用的重要机制之一。Objective To investigate the role of nuclear facto r -κB (NF-κB) in the late phase of cardioprotective effects induced by monophosphoryl lipid A (MLA) preconditioning on ischemia/ reperfusio n (I/R) injury in old rats heart. Methods Ischemic/reperfusi on model of old rats was established. Thirty-six rats were randomly as signed to three groups.Before ischemia/reperfusion rats o f two graps were preconditioned by injection of MLA or DDTC+MLA for 24 hours.At the end of reperfusion, the myocardial infarct size, lactate dehydrogenase (LDH) release,myocytes apoptotic were detec ted. The activaties of NF-κB were detected by using Western blotting method at the 0-min,15-m in, 30-min and 60-min after MLA or DDTC+MLA administration in the other thirty rats. Results The infarct size, released LDH, myocytes apoptotic were respectively reduced signifi cantly in MLA-group than in I/R group(P<0.05 or P<0.01). The activaties of NF-κB rapidly increased at 15 min after MLA pretreatment, come to a head at 30-min,begun to descend at 60-min. The protective effects of MLA were comple tely abolished by NF-κB inhibitor DDTC,simultaneity the activation of NF- κB elici ted by MLA were effectively abrogated. Conclusions MLA precond itioning can prot ect the heart by reducing myocytes apoptotic and myocardial infarct size in old rats. This cardioprotective effect may be attributed to upregulation of the ac tivation of activities of NF-κB.

关 键 词：心肌缺血/再灌注损伤 老年大鼠 MLA NF-κB活性 NF-κB抑制剂 心肌梗死范围 延迟保护作用 细胞凋亡率 DDTC 特异性抑制剂 核转录因子 乳酸脱氢酶 时间依赖性 心肌预处理 药物预处理 24h 损伤模型 方法建立 大鼠心肌 长时间 

分 类 号：R654.2[医药卫生—外科学] R285.5[医药卫生—临床医学]