INTRODUCTION: Several studies have revealed the adverse effect of one-lung ventilation (OLV) on pulmonary function. Nuclear factor-kappa B (NF-κB) is a principal transcription factor of proinflammatory genes. This study was designed to investigate the role of NF-κB in OLV-mediated lung injury. METHODS: Male rabbits, weighing 2.2 ± 0.3 kg, were randomly divided into five groups: sham tracheostomized (Sham), OLV (V(T) = 10 ml/kg, FiO(2) = 1.0), two-lung ventilation (TLV, V(T) = 10 ml/kg, FiO(2) = 1.0), OLV preceded by the treatment with NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC, 50 mg/kg, i.v.), and TLV with the PDTC pretreatment. Arterial blood gases, lung pathological changes, and production of proinflammatory cytokines (tumor necrosis factor-α and interleukin-8) were assessed. NF-κB activation was determined by electrophoretic mobility shift assay (EMSA) and western blotting of nuclear NF-κB p65. RESULTS: The OLV significantly decreased the ratio of partial pressure of oxygen and fraction inspired oxygen (PaO(2)/FiO(2)) compared to the Sham group (p < .01). However, the TLV had no evident effect on the PaO(2)/FiO(2) ratio. The pretreatment with PDTC significantly reversed the OLV-induced reduction in the PaO(2)/FiO(2) ratio. The PDTC pretreatment also markedly attenuated the OLV-mediated lung injury and proinflammatory cytokine production. The OLV potentiated the NF-κB DNA binding activity assessed by EMSA and the NF-κB nuclear translocation. The OLV-mediated NF-κB activation was markedly inhibited by the PDTC pretreatment. CONCLUSION: Our data collectively demonstrate that OLV can cause lung injury through the activation of NF-κB and the production of proinflammatory cytokines. Blocking NF-κB reduces lung inflammation and may be an effective strategy in the management of OLV-induced lung damage.
INTRODUCTION: Several studies have revealed the adverse effect of one-lung ventilation (OLV) on pulmonary function. Nuclear factor-kappa B (NF-κB) is a principal transcription factor of proinflammatory genes. This study was designed to investigate the role of NF-κB in OLV-mediated lung injury. METHODS: Male rabbits, weighing 2.2 ± 0.3 kg, were randomly divided into five groups: sham tracheostomized (Sham), OLV (V(T) = 10 ml/kg, FiO(2) = 1.0), two-lung ventilation (TLV, V(T) = 10 ml/kg, FiO(2) = 1.0), OLV preceded by the treatment with NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC, 50 mg/kg, i.v.), and TLV with the PDTC pretreatment. Arterial blood gases, lung pathological changes, and production of proinflammatory cytokines (tumor necrosis factor-α and interleukin-8) were assessed. NF-κB activation was determined by electrophoretic mobility shift assay (EMSA) and western blotting of nuclear NF-κB p65. RESULTS: The OLV significantly decreased the ratio of partial pressure of oxygen and fraction inspired oxygen (PaO(2)/FiO(2)) compared to the Sham group (p < .01). However, the TLV had no evident effect on the PaO(2)/FiO(2) ratio. The pretreatment with PDTC significantly reversed the OLV-induced reduction in the PaO(2)/FiO(2) ratio. The PDTC pretreatment also markedly attenuated the OLV-mediated lung injury and proinflammatory cytokine production. The OLV potentiated the NF-κB DNA binding activity assessed by EMSA and the NF-κB nuclear translocation. The OLV-mediated NF-κB activation was markedly inhibited by the PDTC pretreatment. CONCLUSION: Our data collectively demonstrate that OLV can cause lung injury through the activation of NF-κB and the production of proinflammatory cytokines. Blocking NF-κB reduces lung inflammation and may be an effective strategy in the management of OLV-induced lung damage.