P38 MAPK inhibition reduces myocardial reperfusion injury via inhibition of endothelial adhesion molecule expression and blockade of PMN accumulation
P38 MAPK inhibition reduces myocardial reperfusion injury via inhibition of endothelial adhesion molecule expression and blockade of PMN accumulation
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DOI：
10.1016/s0008-6363(01)00488-6
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发表时间：
2002-02-01
影响因子：
10.8
通讯作者：
Ma, XL
中科院分区：
文献类型：
--
作者：
Gao, F;Yue, TL;Ma, XL
背景资料：体外研究表明，p38丝裂原活化蛋白激酶（p38 MAPK）在中性粒细胞活化和炎性细胞因子产生中起着至关重要的作用。然而. p38 MAPK对心肌再灌注损伤（一种涉及典型炎症反应的病理状态）的作用尚未完全研究。本研究观察了p38 MAPK特异性抑制剂SB 239063对小鼠缺血再灌注（I/R）心肌损伤的影响，并探讨了p38 MAPK抑制剂对I/R心肌损伤的保护作用机制。方法和结果：I/R导致显著的心肌损伤（心肌梗死45+/-2.9%）和显著的PMN积聚（髓过氧化物酶活性1.03+/-0.16 U/100 g组织）。SB 239063的给药显著抑制了心肌炎症反应，这一点通过减少I/R心肌组织中PMN的积聚而得到证实（0.62+/-0.008 U/100 g组织，P
Background: In vitro evidence suggests that the p38 mitogen-activated protein kinase (p38 MAPK) plays a crucial role in PMN activation and inflammatory cytokine production. However. the effect of p38 MAPK on myocardial reperfusion injury, a pathologic condition involving a typical inflammatory response, has not been fully examined. In the present studs, we investigated the effect of SB 239063, a specific p38 MAPK inhibitor, on myocardial injury in a murine ischemia/reperfusion (I/R) model and elucidated the mechanism by which p38 MAPK inhibitor may exert its protective effect against I/R injury. Methods and results: I/R resulted in a significant myocardial injury (myocardial infarct 45+/-2.9%) and marked PMN accumulation (myeloperoxidase activity 1.03+/-0.16 U/100 g tissue). Administration of SB 239063 significantly inhibited the myocardial inflammatory response as evidenced by reduced PMN accumulation in I/R myocardial tissue (0.62+/-0.008 U/100 g tissue, P