Regulation of epithelial sodium channel-γexpression by PPAR-γagonist in mice with LPS-induced ARDS

doi:10.3969/j.issn.1002-1949.2014.08.016

Abstract：Objective To investigate the effect of PPAR -γagonist on the expression of epithelial sodium channel -γ( ENaC-γ) in mice with LPS-induced ARDS.Methods Forty male BALB/C mice were randomly divided into Control group , LPS group, RGZ group and GW9662 group ( n=10 ) .The levels of interleukin -1β( IL-1β) and tumor necrosis factor -α( TNF-α) in the bronchoalveolar lavage fluid ( BALF) were measured by ELISA .The wet-to-dry ratio ( W/D) of the lung tissues was determined to evaluate lung edema .HE staining was used to observe the pathological changes and to assess lung injury scores .The expressions of ENaC -γprotein in lung tissues were detected by immunohistochemistry and Western blotting .The levels of ENaC -γmRNA in the lung tissues were analyzed using RT -PCR.Results Compared with those in Control group , the IL-1βand TNF-αlevels in the BALF, W/D, lung injury scores were significantly increased in LPS group , RGZ group and GW9662 group (P<0.05).Compared with LPS group, the index levels and lung injury scores were significantly decreased in RGZ group ( P <0.05 ).However, there was no statistical difference between LPS group and GW9662 group (P>0.05).Compared with Control group (600 ± 25IOD, 0.64 ±0.01, 0.67 ±0.02), the expressions of ENaC -γprotein and mRNA were significantly decreased in LPS group (210 ±15IOD, 0.18 ±0.02, 0.22 ±0.04; P<0.05), RGZ group (450 ± 30IOD, 0.43 ±0.03, 0.45 ±0.03;P<0.05) and GW9662 group (235 ±35IOD, 0.21 ±0.03, 0.25 ± 0.02;P <0.05).The expression of ENaC -γprotein and mRNA in RGZ group were significantly different from those in LPS group and GW9662 group ( P <0.05 ), but there were no statistical differences between LPS group and GW9662 group (P>0.05).Conclusion PPAR-γagonist may play a protective role in mice with LPS -induced ARDS via up -regulation of ENaC -γat the transcriptional level .