白藜芦醇通过激活SGK1上调急性肺损伤小鼠肺泡上皮钠离子通道的表达  

Resveratrol up-regulates the expression of alveolar epithelial sodium channel in acute lung injury mice via activation of SGK1

作　　者：唐旭毛 戚迪[1] 王导新[1] 

机构地区：[1]重庆医科大学附属第二医院呼吸内科,重庆400010

出　　处：《基础医学与临床》2017年第9期1215-1219,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金(81270141)

摘　　要：目的探讨白藜芦醇(resveratrol)对急性肺损伤(ALI)小鼠肺泡上皮钠离子通道(ENaC)的作用及可能机制。方法将小鼠随机分为对照(control)组、LPS组、RES组和PP242组,每组6只。苏木精-伊红(HE)染色观察肺组织病理;BCA法测肺泡灌洗液(BALF)中蛋白含量,酶联免疫吸附实验(ELISA)检测炎性因子水平;流式细胞计量术检测BALF中性粒细胞比例;Western blot检测肺组织α-ENaC蛋白表达和SGK1磷酸化水平,实时荧光定量PCR(qPCR)检测肺组织α-ENaC mRNA转录水平。结果 1)与对照组相比,LPS组肺组织损伤明显,BALF中性粒细胞比例、蛋白含量和炎性因子水平明显升高(P<0.05),肺组织α-ENaC表达和SGK1磷酸化水平显著下调(P<0.05);2)与LPS组相比,RES组肺损伤明显减轻,BALF中性粒细胞比例、蛋白含量和炎性因子水平明显降低(P<0.05),伴α-ENaC表达和SGK1磷酸化水平显著上调(P<0.05);3)与RES组相比,PP242组肺损伤明显加重,BALF中性粒细胞比例、蛋白含量和炎性因子水平明显升高(P<0.05),同时伴α-ENaC表达和SGK1磷酸化水平显著下调(P<0.05)。结论 SGK1介导的α-ENaC上调机制参与了RES对ALI的保护作用。Objective To investigate the effect of resveratrol on alveolar epithelial sodium channel in acute lung injury mice and the potential mechanism. Methods Twenty-four C57BL,/6 mice were randomly divided into control group, LPS group, RES group and PP242（mTORC inhibitor） group with 6 mice in each group. The pathological changes in lung tissue were evaluated by HE staining; the concentrations of total protein in bronchoalveolar lavage fluid （BALF） were assessed by BCA （ bieinchoninic acid）. The levels of inflammatory cytokines in BALF were determined by ELISA. The proportions of polymorphonuclear neutrophil （PMN） in BALF were detected by Flow Cytometry. The transcription levels of α-ENaC mRNA were assessed by qPCR while the protein levels of α-ENaC and p-GSK1 were measured by Western blot. Results 1 ） Compared with mice in control group, severe pathological lung injury changes were observed in mice of LPS group, with increased total protein levels, PMN proportions,levels of inflammatory eytokines in BALF （ P 〈 0.05 ） , accompanied by down-regulated level of α-ENaC and p-SGK1 in lung tissues （P〈0. 05）. 2）Compared with mice in LPS group, resveratrol significantly reversed lung injury triggered by LPS, decreased total protein levels, PMN proportions, levels of inflammatory cytokines in BALF （P〈0. 05）, with down-regulated levels of α-ENaC and p-SGK1 in lung tissues （P〈0. 05）. 3） However, PP242 prevented beneficial effects of RES on ALI. Conclusions Up-regulation of α-ENaC expression via activation of SGK1 takes part in the protective effects of RES on LPS-induced ALI in mice.

关 键 词：白藜芦醇 急性肺损伤 肺泡上皮钠离子通道 SGK1 

分 类 号：R563.8[医药卫生—呼吸系统]