目的：探讨过氧化物酶增殖体活化受体-γ（ PPAR-γ）激动剂对LPS诱导的小鼠ARDS的保护作用及其对肺泡上皮细胞钠通道-γ亚基（ ENaC-γ）的调控作用。方法40只雄性BALB/C小鼠随机分为对照组（ Control组）、模型组（ LPS组）、罗格列酮治疗组（ RGZ组，LPS＋罗格列酮）及GW9662干预组（ GW9662组，LPS＋GW9662＋罗格列酮），每组10只。处理后收集相关标本，ELISA测定肺泡灌洗液（ BALF）中IL-1β和TNF-α水平。肺组织湿/干比（ W/D）测定肺水肿程度。 HE染色观察肺组织病理变化并进行肺组织损伤评分。用免疫组织化学法和Western blot测定肺组织ENaC-γ蛋白的表达。 RT-PCR测定ENaC-γmRNA的表达。结果与Control组比较，LPS组、RGZ组和GW9662组中IL-1β和TNF-α水平、W/D值、HE染色肺组织损伤程度及评分明显升高（ P＜0．05）；与LPS组比较，RGZ组各指标水平及肺损伤评分明显下降（P＜0．05），但LPS组和GW9662组比较差异无统计学意义（P＞0．05）。 LPS造模后，LPS组（210±15IOD，0．18±0．02，0．22±0．04）、RGZ组（450±30IOD，0．43±0．03，0．45±0．03）、GW9662组（235±35IOD，0．21±0．03，0．25±0．02）肺组织ENaC-γ蛋白和mRNA的表达明显低于Control组（600±25IOD，0．64±0．01，0．67±0．02，P＜0．05），RGZ组与LPS组和GW9662比较差异有统计学意义（P＜0．05），但LPS组和GW9662组比较差异无统计学意义（P＞0．05）。结论 PPAR-γ受体激动剂可能从转录水平上调肺泡ENaC-γ的表达，从而减轻LPS诱导的小鼠ARDS肺水肿程度，发挥保护性作用。%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 .
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