摘要
目的:探讨丝裂原活化蛋白激酶(MAPK)信号通路三亚族ERK,p38,JNK在大鼠高氧性肺损伤动物模型中的表达及作用.方法:24只3周龄Wistar大鼠随机分成4组:空气对照组和高氧暴露3,7和14d组,每组动物6只.高氧暴露组置于常压高氧仓中(O2≥95%),空气对照组置于常压空气中(O2=21%).光镜下观察肺组织病理学改变,采用二步法免疫组化检测磷酸化ERK,p38,JNK在肺组织中的分布.WesternBlot检测磷酸化MAPK蛋白表达变化.结果:高氧暴露3,7d组出现急性肺损伤的典型病理学特征,高氧暴露14d组肺间质及纤维细胞增生明显.免疫组化显示空气对照组仅肺泡上皮细胞及气道上皮细胞见少量磷酸化ERK,p38,JNK阳性表达,高氧暴露组则阳性细胞明显增多,广泛分布于肺内细胞中:肺泡上皮细胞、气道上皮细胞、胸膜间皮细胞、浸润炎细胞及间质纤维细胞,p38阳性表达尤多见于炎性细胞中.WesternBlot显示高氧暴露组较空气对照组磷酸化蛋白表达明显增强,ERK,JNK高氧暴露7d组表达最强(P<0.05),p38在高氧暴露14d组表达最为明显(P<0.05).结论:高浓度氧可激活MAPK信号途径,磷酸化ERK,p38,JNK在高氧损伤肺组织表达明显增加,MAPK三亚族ERK,p38,JNK活性变化在时间上并不具有同步性.
AIM： To investigate the expressions and roles of ERK, p38, JNK, three sub-families of mitogen-activated protein kinase （MAPK） signaling pathway, in hyperoxia-indueed lung injury. METHODS： Twenty-four Wistar rats aged 3 weeks old were randomly divided into 4 groups （ n = 6 ） ： control group, hyperoxia 3, 7, 14 d groups. The rats were kept in oxygen chamber at normal pressure （ O2≥ 95% ） in hyperoxia injury groups, and at normal pressure （O2 =21% ）in control group. The histopathological changes of lung tissues were examined by light microscopy; the locations and quantities of three subfamilies of MAPK were analyzed by immunohistochemistry and Western Blot analysis, respectively. RESULTS： The typical pathological characters of acute lung injury were discovered in hyperoxia 3 and 7 d groups , and pulmonary interstitia hyperplasia and fibrocyte proliferation were found in hyperoxia 14 d group. Although there were rare MAPK positive expression in alveolar and airway epithelial cells in control group, while the positive cells increased strikingly in hyperoxia injury groups. These cells involved in this process included mainly alveolar, airway epithelial ceils, pleural mesothelial cells, infiltrative inflammatory cells, interstitium fibrocytes. The p38 positive cells were detected in a lots of infiltrative inflammatory cells especially. Protein quantities of MAPK were higher in hyperoxia injury groups than those in control group. The expressions of phosphorylated ERK 1/2 and JNK peaked in the hyperoxia 7 d group （P 〈 0. 05 ）, but phosphorylated p38 had the strongest expression in the hyperoxia 14 d group （ P 〈 0. 05 ）.CONCLUSION： The expression of phosphorylated MAPK in lung tissue increases significantly in hyperoxia-induced lung injury and reactive oxygen species activate ERK, p38, JNK of MAPK superfamily; the activity changes of ERK, p38, JNK are not isoehronous.
出处
《第四军医大学学报》
北大核心
2007年第12期1061-1064,共4页
Journal of the Fourth Military Medical University
基金
国家自然科学基金(30370618)
重庆医科大学创新基金(3117-35115)
