丝裂原活化蛋白激酶在一氧化碳抗大鼠肢体缺血再灌注所致肺损伤中的作用  

Role of MAPKs in protection of carbon monoxide against lung injury following limb ischemia-reperfusion in rats

作　　者：周君琳[1] 凌亦凌[2] 鲁士宝[1] 关立[1] 刘清河[1] 王志伟[1] 黄欣莉[2] 

机构地区：[1]首都医科大学附属北京朝阳医院骨科,北京100020 [2]河北医科大学病理生理教研室

出　　处：《中华实验外科杂志》2005年第2期163-165,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目 (30 2 71 337)

摘　　要：目的　观察丝裂原活化蛋白激酶 (MAPKs)在外源性一氧化碳 (CO)抗大鼠肢体缺血再灌注 (IR)所致肺损伤中的作用。方法　健康SD大鼠 ,随机分为 4组 (每组n =8) :对照组 (Con trol)、Control +CO、IR和IR +CO组。复制大鼠双后肢缺血及再灌注后肺损伤模型。IR +CO和Control +CO组在再灌注前 1h或相应时间点置含CO的空气中 ,其余两组呼吸空气。观察大鼠肺组织学、肺组织中中性粒细胞 (PMN )数目、肺组织湿重和干重之比 (W /D)、丙二醛 (MDA)含量以及动物生存情况变化。应用Westernblotting检测肺组织中三种磷化MAPKs ,即细胞外信号调节激酶(ERK)、c Jun氨基末端激酶 (JNK)和 p3 8表达的变化。 结果　与Contorl组相比 ,IR组动物死亡率、肺组织PMN数目、W /D、MDA含量以及磷酸化ERK、JNK和p3 8表达均显著增高 ;与IR组相比 ,IR +CO组IR组动物死亡率、肺组织中PMN数目、W /D和MDA含量均显著降低、肺损伤减轻 ,p3 8表达显著增高 ,JNK表达显著降低 ,ERK表达无显著变化。结论　MAPKs信号通路参与了外源性CO抗大鼠肢体IR所致肺损伤作用的分子机制。Objective To observe the role of mitogen-activated protein kinases (MAPKs) in protection of exogenous carbon monoxide (CO) against lung injury induced by ischemia-reperfusion (IR) of hind limb in rats.Methods Healthy SD rats were randomly divided into 4 groups:control,control+CO,IR and IR+CO.An animal model of ischemia in hind limbs and the reperfusion lung injury was made.The rats in IR+CO and control+CO groups were exposed to air containing CO at 1 h before reperfusion or thecorresponding control time point,while the other two groups were exposed to theroutine air.The lung tissue structure,polymorphonuclear leukocyte (PMN) count,wet-to-dry weight ratio (W/D),malondialdehyde (MDA) content and the animal survival rate were assayed.The phosporylated forms of extracellular-signal regulatedprotein kinase (ERK),c-Jun NH2-terminal kinase (JNK) and p38 MAPKs in the lung were detected by Western blotting.Results Compared with the control group,the animal death rate,lung PMNs number,W/D,MDA content and the activated protein levels of ERK,JNK and p38 were all significantly increased in IR group.As compared with the IR group,the animal death rate,lung PMNs number,W/D,MDA content and the p-JNK protein level were all significantly decreased,while the p-p38 protein level was increased in IR+CO group.There was no significant difference in the p-ERK expression between the IR and IR+CO groups.Conclusion MAPKs pathway might be involved in the protective mechanims of CO against the lung injury induced by limb IR in rats.

关 键 词：肺损伤 肺组织 再灌注 大鼠 表达 IR 肢体缺血 丝裂原活化蛋白激酶 数目 动物 

分 类 号：R563[医药卫生—呼吸系统]