title: [Protection of hyperoxia-induced lung injury by granulocyte-macrophage colony-stimulating factor via RAGE-NF-κB signaling pathway in newborn rats].
abstract: OBJECTIVE
  To explore the effects of granulocyte-macrophage colony-stimulating factor (GMCSF) on hyperoxia exposure lung injury in newborn rats and elucidate its protective mechanism of operating via the signaling pathway of advanced glycation end products (RAGE)-NF-κB.
  
  
  METHODS
  Twenty-four 3-day-old SD rats from 3 litters were randomly divided into 3 groups. They were hyperoxia exposure plus GMCSF group (group A), hyperoxia exposure group (group B) and air exposure group (group C). The rats from groups A and B were placed in a sealed Plexiglas chamber with a minimal in-and-outflow, providing 6 - 7 exchanges per hour of chamber volume and maintaining O(2) levels above 95%. While the rats in group C only were exposed to air simultaneously. The rats in group A received subcutaneous injections of recombinant murine GMCSF (9 µg/kg) during hyperoxia exposure at 24 h, 72 h and 120 h respectively. And the rats in groups B and C received subcutaneous injections of saline vehicle alone at the same time point. Seven days later, all were sacrificed and immunohistochemistry was employed to assess the expression of RAGE in lung tissue. The levels of tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF) and serum samples were detected by ELISA (enzyme-linked immunosorbent assay). The RAGE mRNA and NF-κB mRNA in tissue homogenates were detected by RT-PCR while RAGE and NF-κB by Western blot. Also the values of lung damage score were calculated with microscopic histology.
  
  
  RESULTS
  The value of lung damage score in group C, B and A was 0.46 ± 0.20, 3.06 ± 0.33 and 2.31 ± 0.56 respectively, there was significantly difference among three groups (P = 0.000). The expression of RAGE mRNA and protein in three groups were 0.14 ± 0.02, 0.34 ± 0.06, 0.28 ± 0.04 and 0.30 ± 0.04, 0.76 ± 0.11, 0.55 ± 0.08 respectively. There were both significantly differences among three groups (P = 0.000, P = 0.000). The expression of NF-κB mRNA and protein in three groups were 0.41 ± 0.21, 0.90 ± 0.36, 0.69 ± 0.30 and 0.41 ± 0.26, 0.96 ± 0.43, 0.77 ± 0.33 respectively, there were both significantly difference among three groups (P = 0.000, P = 0.017). The level of TNF-α in BALF was 76 ± 10, 224 ± 42 and 143 ± 24 respectively, there was significantly difference among three groups (P = 0.000). All indicators above in group B and group A were significantly more than those in group C (all P < 0.05), while these indicators in group A were lower than those in group B. But there was no difference in the level of TNF-α of serum among three groups (P > 0.05).
  
  
  CONCLUSIONS
  GMCSF may protect hyperoxia-induced lung injury via down-regulating the signaling pathway of RAGE-NF-κB.
authors.affiliation: Department of Neonateology, Huai'an First Hospital, Nanjing Medical University, Huai'an 223300, China. lyh0729@163.com
authors.forename: Zhao-fang
authors.initials: ZF
authors.lastname: Tian
authors.forename: Zhi-min
authors.initials: ZM
authors.lastname: Zhang
authors.forename: Yu-hong
authors.initials: YH
authors.lastname: Li
authors.forename: Sai
authors.initials: S
authors.lastname: Zhao
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D017127:Glycation End Products, Advanced / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D018496:Hyperoxia / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor