目的 研究体外循环肺组织中P38丝裂原活化蛋白激酶(P38 MAPK)的变化对肺组织炎症反应的作用及其机制.方法 54只SD大鼠随机分为3组:全麻开胸组(S组)、体外循环组(CPB组)、体外循环+SB203580组(SB组).不同时间段处死动物,留取标本,Western blotting检测肺组织中P38 MAPK、磷酸化P38 MAPK.EMSA检测核因子(NF)-κB的DNA结合活性变化,ELIASA分别检测TNF-α和IL-1β产量.结果 CPB组磷酸化P38MAPK较S组增加.NF-κB活性水平也较S组明显增加,肺组织中TNF-α和IL-1β产量增加.SB203580减轻了肺组织中磷酸化P38MAPK活性水平,减少了肺组织中炎症闪子的产生.结论 (1)P38MAPK通过影响NF-κB的激活而参与体外循环术后肺组织炎症因子的产生;(2)SB203580通过阻断P38MAPK的激活而减轻体外循环术后肺炎症因子的产生.%Objective To examine the changes in P38MAPK during and after cardiopulmonary bypass (CPB) and the effect of SB203580, a specific P38MAPK inhibitor, on CPB-induced pulmonary inflammatory response. Metholds Fifty-four SD rats were randomized into 3 groups (each=18), namely sham CPB group, CPB group, and SB203580 group in which rats underwent CPB with SB203580 pretreatment. The lungs were excised immediately after the rats were sacrificed at scheduled time points and p38, nuclear factor-κB (NF-ΚB), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected. Results The activities of P38 MAPK and NF-ΚB were significantly increased in CPB group as compared with those in sham CPB group. CPB resulted in increased TNF-α and IL-1β production in the lung tissues. Administration of SB203580 prevented up-regulation of lung phosphorylated P38 MAPK, and decreased proinflammatory cytokine productions in the lung tissues. Conclusion P38 MAPK is activated in the lung tissue during and after CPB to affect the activation of NF-κB in the lung; SB203580 selectively inhibits P38 MAPK activation to reduce proinflammatory cytokine production after CPB.
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