关键词: 呼吸机所致肺损伤, 核因子-κB, 肿瘤坏死因子-α

Abstract: Objective The expression of tumor necrosis factor-α(TNF-α) and the activation of nuclear factor-kappa B(NF-κB) were examined in order to investigate the molecular mechanism of ventilator-induced lung injury(VILI).Methods The VILI model was established by mechanical ventilation with a VT of 40 mL/kg. Forty healthy male New Zealand rabbits were randomly divided into control group,conventional ventilation group and VILI group.The concentrations of TNF-α in lung homogenate were measured by enzyme-linked immunosorbent assay(ELISA).The TNF-α mRNA was measured by semi-quantitative transcription-polymerase chain reaction(RT-PCR).The DNA-binding activity of NF-κB was detected by electrophoretic mobility shift assay(EMSA).The partial arterial blood pressure of oxygen(PaO₂),wet lung weight to dry lung weight ratio(W/D) and histological changes of lung tissue were also investigated. Results 1) After 4 h of injurious ventilation,PaO₂ was significantly reduced compared with conventional ventilation group(P<0.05).In contrast,the W/D was significantly increased compared with control group(P<0.01) and conventional ventilation group(P<0.01).2) The concentrations of TNF-α proteins in lung homogenates were significantly increased by the injurious ventilation for 2 h or 4 h,compare to control group and conventional ventilation group (all P<0.01).The TNF-α mRNA levels in all injurious ventilation groups were significantly higher than control group(all P<0.01) and conventional ventilation group((P<)(0.01)).The TNF-α mRNA levels induced by injurious ventilation for 4 h were significantly higher than that induced by injurious ventilation for 1 h(P<0.01) and 2 h(P<0.05).3) The DNA-binding activity of oxymatrine was significantly increased in all injurious ventilation groups compared with that of control and conventional ventilation group(P<0.01).The DNA-binding activity of NF-κB reached to maximal level at 2 h and remained until 4 h.Conclusion The mRNA and protein level of TNF-α and DNA binding activity of NFκB were up-regulated by VILI.Increased NF-κB activity in the lung may be involved in the transcriptional up-regulation of TNF-α.

Key words: ventilator-induced lung injury, nuclear factor-kappa B, tumor necrosis factor-α