MG-132对高氧肺损伤中细胞凋亡的保护作用及对p38信号通路的影响

目的 探讨泛素蛋白酶体抑制剂MG-132对高氧诱导的大鼠损伤肺组织中细胞凋亡及p38信号通路激活的保护作用。 方法 将26只SD大鼠随机分为四组：正常对照组（n=5）、MG-132对照组（n=5）、高氧组（n=8）和MG-132高氧组（n=8）。制备高氧肺损伤动物模型，MG-132处理组给予蛋白酶体抑制剂0.5 mg/kg，1次/d，腹腔注射。所有大鼠行肺组织病理学检查；采用TUNEL法检测细胞凋亡；免疫组织化学法检测泛素化蛋白和p38蛋白的表达。 结果 高氧暴露的SD大鼠肺组织可见水肿、大量炎症细胞浸润等急性炎症反应。高氧组的凋亡指数、p38MAPK表达均高于正常对照组和MG-132高氧组（P<0.05或P<0.01）。 结论 高氧可以导致肺组织细胞发生凋亡，可能是通过激活p38MAPK信号通路来调控的。蛋白酶体抑制剂MG-132可以减轻高氧引起的肺损伤，可能对p38MAPK信号通路有抑制作用。

Protective effects of MG-132 on p38 signaling pathway and cell apoptosis in lung injury induced by hyperoxia

Objective To investigate the protective effects of the ubiquitin proteasome inhibitor MG-132 on p38 signaling pathway and apoptosis in lung injury induced by hyperoxia. Methods Twenty-six SD rats were randomly divided into 4 groups: normal control group (n=5), MG-132 control group (n=5), hyperoxia group (n=8) and MG-132 hyperoxia group (n=8). Hyperoxia lung injury rat models were established, and proteasome inhibitor (0.5 mg/kg) was intraperitoneally injected in control group and MG-132 hyperoxia group once daily. The resected lungs were histopathologically examined, and cell apoptosis and expression of ubiquitin and p38 were detected by TUNEL and immunohistochemistry, respectively. Results After hyperoxia exposure, there were edema and inflammatory cell infiltration in the lung tissues of SD rats. The apoptosis index and expression of p38MAPK of hyperoxia group were higher than those of normal control group and MG-132 hyperoxia group (P<0.05 or <0.01). Conclusion High oxygen can induce cell apoptosis and may activate p38MAPK signaling pathway. The proteasome inhibitor MG-132 can reduce the lung injury induced by hyperoxia and inhibit P38MAPK signaling pathway.