p38MAPK参与去甲肾上腺素预处理的延迟保护作用

The Late Phase of Monophosphoryl Lipid A Preconditioning Is Related to the Activities of p38 MAPK in Rats

目的 探讨p38MAPK(丝裂素活化蛋白激酶)是否参与去甲肾上腺素(NE)预处理的延迟保护作用。方法 建立大鼠心肌缺血/再灌注损伤(I/R)模型。分别应用去甲肾上腺素、p38的特异性抑制剂SB203580预处理心脏,24h后对心脏进行缺血再灌注,观察此时心肌梗塞范围、血浆乳酸脱氢酶(LDH)活性,同时用western blotting方法检测NE预处理后即刻、10 min、15 min、30 min时p^(38)磷酸化水平。结果 NE预处理明显缩小心梗范围,减轻血浆LDH活性升高程度(P<0.01 vs I/R)。p38磷酸化在NE预处理后即刻稍微增高,10min轻度升高,15min达到高峰,30min开始下降。用SB203580可明显抑制p38磷酸化,而心梗范围、血浆LDH活性同单纯缺血/再灌注组相似(P>0.05)。结论 ①去甲肾上腺素预处理对24h后缺血/再灌注心肌有保护作用。②p38参与心肌预处理后的延迟保护作用,去甲肾上腺素预处理后p38短暂而快速的激活可能是药物延迟保护作用的重要机制之一。

Objective To investigate the role of p38MAPK in the late phase of cardioprotective effects induced by norepinephrine preconditioning(NE-P) on ischemia/reperfusion (I/R) injury in rat heart. Methods TheI/R model of rats was established. Eighteen rats were randomly assigned to three groups: I/R group. NE-P group: Sixrats received injection of norepinephrine 24h prior to 30 min of ischemia followed by 120 min of reperfusion. SB203580 +NE group: Six rats received SB203580 10min prior to NE administration. At the end of reperfusion, the myocardial infarct size and LDH release were detected. The activities of p38MAPK were detected using a western blotting methodat the 0min, 10min, 15min, 30min after NE administration in other eighteen rats. Results The infarct size, released LDH were respectively reduced sigaificantly in NE-P group (P<0.05 versus I/R group). The activities of p38MAPK rapidly increased at 10 min after NE-P, come to a peak at 15min,begun to descend at 30min (respectively P<0.05 versus at 0 min). The protective effects of NE were completely abolished by p38MAPK inhibitor SB203580, simultaneously, the activation of p38MAPK elicited by NE were effectively abrogated. Conclusion NE preconditioning can protect the heart by reducing myocardial infarct size in rats. This cardioproteetive effect might be attributed to upregulation of activities of p38MAPK.