MAPKs在硫化氢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 Hydrogen Sulfide against Lung Injury Following Limb Ischemia-reperfusion in Rats

作　　者：刘洋[1] 单磊[1] 黄新莉[2] 刘清和[1] 陆铁[1] 周君琳[1] 

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,河北石家庄050017

出　　处：《昆明医学院学报》2011年第9期16-20,共5页Journal of Kunming Medical College

基　　金：国家自然科学基金资助项目(1070050;30800440);北京市自然科学基金资助项目(7092035)

摘　　要：目的观察丝裂原活化蛋白激酶(MAPKs)在外源性硫化氢(H2S)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,随机分为四组(每组n=8):对照组(Control),Control+NaHS组,IR组和IR+NaHS组.应用双大腿根部止血带复制大鼠双后肢缺血及再灌注后肺损伤模型.Control和IR组动物分别于再灌注前10 min和相应的对照时间点腹腔注射无菌生理盐水(0.5 mL/kg);IR+NaHS和Control+NaHS组动物分别于再灌注前10 min和相应的对照时间点腹腔注射NaHS(28μmol/kg);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等变化.应用Westernblotting检测肺组织中三种磷酸化MAPKs-细胞外信号调节激酶(ERK)、c-Jun氨基末端激酶(JNK)和p38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p38表达均显著增高(P<0.05);与IR组相比,IR+NaHS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,磷酸化ERK表达显著增高、p38表达显著降低(P<0.05),JNK表达无显著变化.结论 MAPKs信号通路参与了外源性H2S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 hydrogen sulfide（H2S）against lung injury induced by ischemia-reperfusion（IR）of hind limbs in rats.Methods A rat model of limb ischemia was made by tourniquets placed on both hind limbs at a site proximal to trochanter major and the lung injury was induced following reperfusion.Adult male Spraguce-Dawley（SD）rats were randomly divided into four groups（n=8 per group）：Control,Control＋NaHS,IR and IR＋ NaHS.The rats in IR＋NaHS group and Control＋NaHS group were treated with NaHS（28 μmol/kg ip）.The rats in the IR group and the Control group were treated with equal volume of drug vehicle（Normal saline,0.5 mL/kg）.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 phosphorylated forms of extracellular-signal regulated protein kinase（ERK）,c-Jun NH2-terminal kinase（JNK）and p38 MAPKs in the lung were detected by Westernblotting.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.Compared with the IR group,the animal death rate,lung PMNs number,W/D,MDA content and the p-p38 protein level were all significantly decreased,while the p-ERK protein level was increased in IR＋NaHS group.There was no significant difference in the p-JNK expression between the IR group and IR＋NaHS group.Conclusion MAPKs pathway is involved in the protective mechanims of H2S against the lung injury induced by limb IR in rats.

关 键 词：丝裂原活化蛋白激酶 硫化氢 再灌注损伤 肢体 肺 

分 类 号：R392.11[医药卫生—免疫学]