N-myc下游调节基因-2过表达对大鼠肺缺血再灌注损伤的影响

Over-expression of N-myc Downstream Regulated Gene 2 Improves Lung Ischemia-reperfusion Injury in Rats

目的:研究N-myc下游调节基因-2(NDRG2)过表达对大鼠肺缺血再灌注损伤的保护作用。方法:以肺缺血再灌注损伤为模型,将已转染的过表达NDRG2重组腺病毒经气管滴注的方法使大鼠肺泡上皮细胞NDRG2过表达。用Western-blot法检测大鼠肺组织内目的蛋白过表达情况。用ELISA法检测白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)以及白细胞介素-6(IL-6)的水平,肺组织湿干重比值(W/D)检测肺组织的水肿,双荧光素酶报告系统检测核转录因子kappa B(NF-κB)的活性,HE染色检测肺组织病理变化。结果:在肺缺血再灌注损伤中,过表达NDRG2可抑制炎症因子l L-1β、TNF-α以及IL-6的表达,明显减轻肺水肿,抑制NF-κB的活性和病理组织的炎性改变。结论:NDRG2过表达可减轻缺血再灌注所致急性肺损伤,这可能与其抑制炎症反应有关。

Objective： To investigate the protective effect of NDRG2 over-expression on the lung ischemia-reperfusion injury（LIRI） in rats. Methods： The acute alveolar epithelial cell injury model was established by stimulation with LIRI. In order to over-express NDRG2, the lung tissues were transferred with recombinant adenovirus via tracheal instillation method. The concentrations of IL-1β,TNF-α and IL-6 were detected by ELISA. Pulmonary edema was measured by wet-to-dry weight ratio. The transcriptional activity of NF-κB was measured by dual-luciferase reporter assay system. The effects of NDRG2 on lung ischemia-reperfusion induced lung pathological changes were examined. Results： Compared with the control group, NDRG2 over-expression could decrease the releases of IL-1β,TNF-α and IL-6 stimulated by LIRI. The lung wet-to-dry weight ratio was markedly decreased by NDRG2 over-expression. The over-expression NDRG2 inhibited the transcriptional activity of NF-κB and the pathological changes in the lung. Conclusions： NDRG2 over expression could attenuate the inflammatory reactions in LIRI, which played a protective role against the acute damage of the alveolar epithelial cells.