title: Nuclear factor-kappa B mediates one-lung ventilation-induced acute lung injury in rabbits.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of Shantou University Medical College, Shantou, China. zhijianyou2010@yahoo.cn
authors.forename: Zhijian
authors.initials: Z
authors.lastname: You
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.forename: Hongxia
authors.initials: H
authors.lastname: Xu
authors.forename: Minghua
authors.initials: M
authors.lastname: Cheng
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Li
authors.forename: Mingxiu
authors.initials: M
authors.lastname: Kan
authors.forename: Shanglong
authors.initials: S
authors.lastname: Yao
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D011759:Pyrrolidines / Q000494:pharmacology; D011817:Rabbits; D012121:Respiration, Artificial / Q000009:adverse effects; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D018836:Inflammation Mediators; D016209:Interleukin-8; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid; D010100:Oxygen