摘要
目的:观察高氧暴露下肺组织细胞凋亡和磷酸化c-Jun氨基末端激酶(p-JNK)蛋白表达的变化,并探讨JNK信号转导通路对高氧诱导的肺细胞凋亡的调控机制.方法:48只3 wk龄Wistar大鼠随机分为空气对照组、高氧暴露3,7,14d组、空气+JNK抑制剂干预组、高氧暴露7 d+JNK抑制剂干预组.光镜下观察肺组织病理学改变,末端标记法(TUNEL)分析肺组织细胞凋亡的变化,免疫组化检测肺组织p-JNK的表达分布,Western Blot检测肺组织p-JNK蛋白质的表达含量.结果:与空气对照组比较,高氧暴露各时间点组肺组织出现典型急、慢性肺损伤的病理学改变,肺组织细胞凋亡指数和p-JNK蛋白表达含量均显著增加(P<0.05),肺组织p-JNK阳性细胞明显增多.JNK抑制剂SP600125在空气和高氧暴露下均能明显阻断JNK的激活(P<0.05),SP600125干预后高氧暴露肺组织细胞凋亡指数显著减少(P<0.05).结论:细胞凋亡是高氧肺损伤的一个重要病理组织学特点.JNK信号转导通路在高氧肺损伤中被激活,可能发挥促细胞凋亡效应.
AIM： To observe the changes of lung cell apoptosis and the expression of phosphorylated c-Jun NH2-terminal kinase （p-JNK） protein during hyperoxia exposure, and to investigate the regulatory mechanism of JNK signal transduction pathway on hyperoxia-induced lung cell apoptosis. METHODS： Forty-eight Wistar rats aged 3 wk were randomly divided into 6 groups （ n = 8） ： room-air group,3,7,14 d hyperoxia exposure groups, roomair with inhibitor of JNK intervention group, 7 d hyperoxia exposure with inhibitor of JNK intervention group. The histopathological changes of lung tissues were examined by light microscope. The extents of lung cell apoptosis were analyzed by terminal deoxynucleotidyhransferase-mediated dUTP nick end labeling （TUNEL） assay. The distributions and the protein levels of p- JNK were measured by immunohistochemistry and Western Blot analysis, respectively. RESULTS ： The typical pathologic characters of acute and chronic lung injury were discovered in hyperoxia exposure groups. The cell apoptotic index and the p-JNK protein levels of lung tissues both significantly increased in hyperoxia exposure groups compared with those in room-air group（ P 〈 0.05 ）. The p-JNK positive cells increased strikingly in hyperoxia exposure groups compared with those in room-air group. SP600125, the specific inhibitor of JNK, significantly inhibited JNK activity both in room-air and hyperoxia exposure groups （ P 〈 0.05 ）. The cell apoptotic index of lung tissues under hyperoxia exposure reduced markedly after intervention with SP600125 （ P 〈 0.05 ）. CONCLUSION： Cell apoptosis is an important histopathologic feature of hyperoxia-induced lung injury. The activation of JNK signal transduction pathway may initiate under hyperoxla stress and maybe play a role in promoting lung cell apoptosis in hyperoxia-induced lung injury.
出处
《第四军医大学学报》
北大核心
2008年第12期1067-1070,共4页
Journal of the Fourth Military Medical University
基金
国家自然科学基金(30370618)
