title: [Effect of thalidomide in a mouse model of paraquat-induced acute lung injury and the underlying mechanisms].
abstract: OBJECTIVE
  To investigate the intervention effect of thalidomide on paraquat-induced acute lung injury in mice and its mechanism.
  
  
  METHODS
  Male ICR mice were randomly allocated to negative control group (n = 30), thalidomide control group (n = 30), paraquat poisoning group (n = 30), 50 mg/kg thalidomide treatment group (n = 30), 100 mg/kg thalidomide treatment group (n = 30), and 150 mg/kg thalidomide treatment group (n = 30). The negative control group was intraperitoneally injected with the same volume of saline; the thalidomide control group was intraperitoneally injected with thalidomide (150 mg/kg); the paraquat poisoning group was intraperitoneally injected with diluted paraquat solution (22 mg/kg); each thalidomide treatment group was intraperitoneally injected with the same volume of paraquat solution (22 mg/kg) and was injected with thalidomide (50, 100, or 150 mg/kg) 1 h later. All mice were anesthetized and sacrificed at 1, 3, or 7 d after paraquat poisoning, and their lung tissue was collected. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in lung tissue were measured by double-antibody sandwich ELISA; the mRNA expression of nuclear factor-kappa B (NF-κB) was measured by RT-PCR; the protein expression of nuclear NF-kgr;B p65 was measured by Western blot. The pathological changes of lung tissue were observed under light microscope; the wet/dry ratio of the lung was calculated.
  
  
  RESULTS
  Compared with the negative control group, the paraquat poisoning group had significantly increased levels of TNF-α, IL-1β, IL-6, NF-κB mRNA, and nuclear NF-κB p65 and wet/dry ratio of the lung (P < 0.05). Compared with the paraquat poisoning group, the thalidomide treatment groups had significantly decreased levels of TNF-α, IL-1β, IL-6, NF-κB mRNA, and nuclear NF-κB p65 and wet/dry ratios of the lung (P < 0.05), and the 150 mg/kg thalidomide treatment group showed the most significant decrease in the levels of TNF-α, IL-1β, IL-6, NF-κB mRNA, and nuclear NF-κB p65. The observation of pathological changes showed that the paraquat poisoning group had the most marked lung tissue damage at 3 d after poisoning, and the lung tissue damage was lessened in the thalidomide treatment groups.
  
  
  CONCLUSIONS
  Thalidomide can reduce paraquat-induced acute lung injury and lung edema. The mechanism may include inhibition of NF-κB activation and expression and downregulation of TNF-α, IL-1β, and IL-6.
authors.affiliation: Emergency Department of the First Affiliated Hospital of Wenzhou Medical College, Wenzhou Zhejiang Province, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Li-yan
authors.initials: LY
authors.lastname: Xu
authors.forename: Zi-juan
authors.initials: ZJ
authors.lastname: Chang
authors.forename: Guang-ju
authors.initials: GJ
authors.lastname: Zhao
authors.forename: Chao
authors.initials: C
authors.lastname: Nan
authors.forename: Zhong-qiu
authors.initials: ZQ
authors.lastname: Lu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D010269:Paraquat / Q000506:poisoning*; D013792:Thalidomide / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D016207:Cytokines; D052002:NF-kappa B p50 Subunit; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; C073701:Nfkb1 protein, mouse; D013792:Thalidomide; D010269:Paraquat