title: [Effects of simvastatin on lipopolysaccharide induced α-subunit epithelial sodium channel mRNA in rat lung alveolar type II epithelial cells].
abstract: OBJECTIVE
  To study the impact of simvastatin on α-subunit epithelial sodium channel (α-ENaC) mRNA expression in primary culture alveolar typeII (ATII) epithelial cell of rats induced by lipopolysaccharide (LPS) in vitro.
  
  
  METHODS
  ATII of primary generation were isolated from adult Sprague-Dawley (SD) rats. The cells were randomly divided into five groups: blank control group, LPS injured group (final concentration  of  LPS 1 mg/L), simvastatin  low  and  high  concentration groups (final  concentration  of  simvastatin 20 μmol/L, 30 μmol/L, respectively), solution control group. Then, after being intervened for 1, 12 and 24 hours, the level of human tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were monitored by enzyme-linked immunosorbent assay (ELISA), and α-ENaC mRNA expression was tested by reverse transcription-polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  After being intervened for 1, 12 and 24 hours, expressions of TNF-α and IL-1β in LPS injured group were obviously higher than those in blank control group. Expressions of TNF-α and IL-1β at 1, 12 and 24 hours in simvastatin low concentration group were significantly decreased compared with those in LPS injured group (TNF-α 1 hour: 1178.80±127.43 ng/L vs. 2336.00±170.04 ng/L, 12 hours: 1003.60±59.61 ng/L vs. 2479.80±210.41 ng/L, 24 hours: 695.80±25.24 ng/L vs. 1167.60±132.72 ng/L; IL-β 1 hour: 285.00±42.60 ng/L vs. 429.60±27.39 ng/L, 12 hours: 238.60±24.12 ng/L vs. 822.20±12.74 ng/L, 24 hours: 213.40±17.87 ng/L vs. 637.60±22.96 ng/L, all P<0.05). Expressions of TNF-α and IL-1β in high concentration group were decreased more obviously than those in low concentration group (TNF-α 1 hour: 965.60±24.45 ng/L vs. 1178.80±127.43 ng/L, 12 hours: 522.80±16.89 ng/L vs. 1003.60±59.61 ng/L, 24 hours: 252.40±17.64 ng/L vs. 695.80±25.24 ng/L; IL-1β 1 hour: 225.60±34.44 ng/L vs. 285.00±42.60 ng/L, 12 hours: 190.60±17.64 ng/L vs. 238.60±24.12 ng/L, 24 hours: 152.80±14.70 ng/L vs. 213.40±17.87 ng/L, all P<0.05), but increased compared with those in blank control group. After being intervened for 1 hour, no evident changes were observed in expression of α-ENaC mRNA in all groups. After being intervened for 12 hours and 24 hours, evident decrease in expression of α-ENaC mRNA (A value) was observed in LPS injured group compared with blank control group (12 hours: 0.211±0.021 vs. 0.496±0.027, 24 hours: 0.253±0.030 vs. 0.482±0.030, both P<0.05). Expressions of α-ENaC mRNA in simvastatin low concentration group evidently increased compared with those in LPS injured group (12 hours: 0.363±0.030 vs. 0.211±0.021, 24 hours: 0.309±0.024 vs. 0.253±0.030, both P<0.05). Expressions of α-ENaC mRNA in simvastatin high concentration group increased more obviously  compared  with  those  in  low  concentration  group (12 hours: 0.413±0.034 vs. 0.363±0.030, 24 hours: 0.346±0.024 vs. 0.309±0.024, both P<0.05), but decreased compared with blank control group. No evident difference in expressions of all indexes in solution control group was observed compared with those in blank control group.
  
  
  CONCLUSIONS
  High dose simvastatin could improve α-ENaC mRNA expression in primary culture ATII epithelial cells of rats. This may act by modulation the level of TNF-α and IL-1β.
authors.affiliation: Department of Critical Care Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Pei-ying
authors.initials: PY
authors.lastname: Liu
authors.forename: Dao-miao
authors.initials: DM
authors.lastname: Xu
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053503:Epithelial Sodium Channels; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C440894:Scnn1a protein, rat; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin