P38丝裂原活化蛋白激酶在促红细胞生成素后处理减轻再灌注损伤肺细胞凋亡中的作用  

Effects of P38MAPK on Erythropoietin Postconditioning Attenuating Pneumocyte Apoptosis after Lung Ischemia /Reperfusion Injury

作　　者：陈海娥[1] 金晓盛 宋冬[1] 何金波[1] 应磊[1] 游昕[3] 王万铁[1] 

机构地区：[1]温州医科大学缺血一再灌注损伤研究所,浙江温州325035 [2]温州市人民医院呼吸内科,浙江温州325000 [3]解放军第四五四医院胸心外科,南京210002

出　　处：《中国药学杂志》2014年第10期833-836,共4页Chinese Pharmaceutical Journal

基　　金：全军医药卫生科研项目(10MA052);浙江省中医药重点学科建设计划(2012-XK-A28);温州市科技计划一般项目(Y20120001)

摘　　要：目的探讨P38丝裂原活化蛋白激酶(P38MAPK)在促红细胞生成素(EPO)后处理减轻缺血/再灌注损伤大鼠肺细胞凋亡中的作用。方法雄性SD大鼠随机分成5组(n=8),即对照组(C组)、肺缺血/再灌注组(I/R组)、肺缺血/再灌注+促红细胞生成素组(促红细胞生成素组)、促红细胞生成素+溶剂对照组(D组)、促红细胞生成素+SB203580组(SB组)。分别于再灌注2h颈动脉取血、留取左肺组织,检测血清超氧化物歧化酶(SOD)、丙二醛(MDA)、髓过氧化物酶(MPO),光镜观察肺组织形态学结构改变,并进行肺组织损伤定量评估(IQA);原位末端标记法(TUNEL)检测肺细胞凋亡情况并计算凋亡指数(AI)。结果与对照组相比,肺缺血/再灌注组血清超氧化物歧化酶活性显著降低,丙二醛含量、髓过氧化物酶活力显著升高(P<0.01),肺组织损伤定量评估和凋亡指数均显著升高(P<0.05或P<0.01),光镜下肺组织结构发生明显损伤;促红细胞生成素组、促红细胞生成素+溶剂对照组、SB203580组与肺缺血/再灌注组相比,丙二醛含量、髓过氧化物酶活力显著降低,超氧化物歧化酶活性升高(P<0.05或P<0.01),肺组织损伤定量评估和凋亡指数均显著降低(P<0.05或P<0.01),光镜下肺组织结构损伤情况有所改善;促红细胞生成素+溶剂对照组与促红细胞生成素组比较各项指标均无明显差异(P均>0.05);SB203580组与促红细胞生成素组相比,丙二醛含量、髓过氧化物酶活力显著降低,超氧化物歧化酶活性升高(P<0.05或P<0.01),肺组织损伤定量评估和凋亡指数均显著降低(P<0.05或P<0.01),光镜下肺组织结构未见明显损伤。结论促红细胞生成素可以通过减轻肺组织过度氧化应激,肺内中性粒细胞聚集,抑制P38丝裂原活化蛋白激酶激活,改善I/R引起的肺组织结构破坏和肺细胞凋亡。OBJECTIVE To investigate the effects of P38MAPK on erythropoietin（ EPO） postconditioning attenuating pneumocyte apoptosis after lung ischemia / reperfusion injury（ LIRI） in rats. METHODS Adult male Sprague-Dawley rats were randomly divided into 5 groups based upon the intervention（ n = 8） ： control group（ C）,LIRI group（ I / R）,LIRI ＋ EPO group（ EPO）,EPO ＋ solution countrl group（ D）,EPO ＋ SB203580 group（ SB）. At the end of the experiment,blood specimens drawn from the arteria carotis were tested for the content of malondialdehyde（ MDA）,the activity of superoxide dismutase（ SOD） and myeloperoxidase（ MPO）. The histological structure of the left lung was observed under light microscope,and scored by alveolar damage index of quantitative assessment（ IQA）. The pneumocyte apoptosis index（ AI） was achieved by terminal deoxynucleotidyl transferase mediated dUTP nick end abeling（ TUNEL）. RESULTS Compared with C group,in I / R group IQA,AI and MDA level,MPO activity were significantly increased,SOD activity was reduced（ P 0. 05 or P 0. 01）,and morphological abnormality occurred in lung tissue. Compared with I / R group,IQA,AI and MDA level,MPO activity were significantly decreased,SOD activity was improved（ P 0. 05 or P 0. 01）, and morphological abnormality in lung tissue was obviously reduced in EPO,D and SB groups. There were no siginificant difference in all of the indexes between D and EPO groups（ P 0. 05）. However,compared with EPO group,SOD activity was increased（ P 0. 05 or P 0. 01）,the other indexes were obviously reduced,and the abnormal changes of the morphology in I / R were also improved markedly in SB group. CONCLUSION EPO may attenuate pneumocyte apoptosis in LIRI by reducing oxidant generation,neutrophils filtration,then inhibiting activation of P38 MAPK.

关 键 词：缺血 再灌注 促红细胞生成素 超氧化物歧化酶 丙二醛 髓过氧化物酶 细胞凋亡 P38MAPK 

分 类 号：R363[医药卫生—病理学]