核因子-κB对大鼠烧伤早期中性粒细胞在肺组织聚集中的作用

Effect of NF-κB activation on PMN aggregation in rat lung in early stage of burn injury

目的:探讨大鼠烧伤早期肺组织核因子-κB(NF-κB)活化对中性粒细胞(PMN)在肺组织中聚集和发生损害作用的影响。方法:用Wistar大鼠Ⅲ°35%TBSA烧伤模型。实验分正常大鼠对照组、烧伤组、烧伤后吡咯烷二硫代氨基甲酸盐(PDTC)干预组。凝胶电泳迁移率分析法检测肺组织NF-κB活性;逆转录-聚合酶链式反应(RT-PCR)检测白细胞介素8(IL-8)和细胞间黏附分子-1(ICAM-1)mRNA的表达;并测定肺组织髓过氧化物酶(MPO)活性和肺微血管von Willebrand因子(vWF)含量。结果:大鼠烧伤后肺组织NF-κB活性在伤后1h内即迅速增高,并持续增高到伤后24h。伤后肺组织ICAM-1和IL-8mRNA表达、MPO活性均明显高于、肺微血管vWF含量低于对照组。PDTC处理显著缓解上述变化。结论:严重烧伤后肺组织NF-κB活化,从而启动细胞黏附因子和趋化因子的合成和释放,导致PMN在肺组织中聚集,引起肺血管组织细胞损伤。

AIM： To investigate the effect of NF - κB activation on PMN aggregation in rat lung during early stage of burn injury. METHODS： Wistar rats were randomly divided into three groups, i.e. control, burn and PDTC （pyrrolidine dithioncarbamate） treatment groups. The normal rats were taken as control, burn rats underwent 35% TBSA full - thickness burns. Activation of pulmonary NF - κB at 1, 3, 6, 12 and 24 h postburn was tested by electrophoretic mobility shift assay （EMSA）. Expressions of pulmonary IL-8, ICAM- 1 mRNA at 3, 6, 12, 24 h postburn were determined by reverse transcription polymerase chain reaction （RT- PCR）. Meanwhile, the activity of pulmonary myeloperoxidase and the contents of yon Willebrand factor （vWF） in pulmonary microvessels were assayed. RESULTS： Compared to that in control group, the activity of rat pulmonary NF - κB was markedly increased at 1 h postburn, remained this level within 24 h posthurn. The expressions of pulmonary IL - 8, ICAM - 1 mRNA and activity of pulmonary myeloperoxidase incrased, but the contents of vWF in pulmonary microvessels decreased. PDTC （ an antioxidants） effectively inhibited rat pulmonary NF - κB activation, expression of pulmonary IL - 8 and ICAM - 1 mRNA, decreased the activity of pulmonary myeloperoxidase and elevated the contents of vWF in pulmonary microvessels after burn injury. CONCLUSION： Severe burn might activate pulmonary NF - κB, which ultimately leads to the secretion of cytokines, PMN aggregation in lung and pulmonary vascular endothelial injury consequently.