PI3K/Akt信号通路上调急性肺损伤大鼠肺泡上皮钠通道表达

目的 探讨PI3K/Akt信号通路对急性肺损伤(ALI)大鼠肺泡上皮钠通道(ENaC)α、β和γ亚基表达的影响.方法 成年SD大鼠随机分为对照组、ALI组(脂多糖)、胰岛素组及渥曼青霉素组,每组5只.观察肺组织病理改变,收集支气管肺泡灌洗液(BALF),测量总肺水含量,RT-PCR和Western blot测定ENaC mRNA和蛋白、p-Akt表达.结果 胰岛素组BALF蛋白含量、髓过氧化物酶(MPO)活性、总肺水含量较ALI组显著减少(P＜0.05),渥曼青霉素组BALF蛋白含量、MPO活性及总肺水含量较胰岛素组显著增加(P＜0.05).ALI组α-、β-和γ-ENaC蛋白表达显著低于对照组(0.33 ±0.06 vs 1.27 ±0.07,0.18±0.04 vs 0.72±0.04,0.37±0.04 vs0.69±0.05)(P＜0.05).胰岛素组蛋白表达α-ENaC(2.19 ±0.04)、β-ENaC(1.18 ±0.07)和γ-ENaC(1.18 ±0.08)显著高于ALI组(P＜0.05).渥曼青霉素组蛋白表达α-ENaC(0.86 ±0.09)、β-ENaC (0.58±0.05)和γ-ENaC (0.59±0.02)显著低于胰岛素组(P＜ 0.05).胰岛素组ENaC mRNA和p-Akt较ALI组显著升高(P＜0.05).渥曼青霉素组ENaC mRNA和p-Akt较胰岛素组显著降低(P＜0.05).结论 激活H3K/Akt通路上调3种ENaC亚基表达,从而清除肺水肿液.

PI3K/Akt signaling pathway up-regulates the expression of alveolar epithelial sodium channel in acute lung injury rats

Abstract:Objective To investigate the role of PI3K/Akt signaling pathway on expression of alveolar epithelial sodium channel(ENaC) in LPS-induced acute lung injury (ALI). Methods Healthy adult Sprague-Dawley (SD) rats were randomly divided into control group, ALI group(LPS) ,treatment group(LPS+insulin), intervention group(LPS+insulin+wortmannin) with 5 rats in each group. The pathological changes in lung were observed, total lung water content(TLW) were measured, bronchoalveolar lavage fluid(BALF) were collected,and the mRNA and protein levels of ENaC and level of p-Akt were determined by RT-PCRand Western blot. Results Protein level and MPO activity in BALF and TLW in treatment group was significantly lower than that in ALI group (p＜0.05); Protein level and MPO activity in BALF and TLW in intervention group was significantly higher than that in treatment group (p＜0.05). The mRNA and protein levels of ENaC and level of p-Akt in treatment group were significantly higher than that of ALI group (p＜0.05); The mRNA and protein levels of ENaC and level of p-Akt in intervention group were significantly lower than that of treatment group (p＜0.05). Conclusion Activation of PI3K/Akt signaling pathway up-regulates the expression of ENaC to clear the pulmonary edema fluid.