吉林大学学报(医学版) ›› 2015, Vol. 41 ›› Issue (04): 716-720.doi: 10.13481/j.1671-587x.20150409

• 基础研究 • 上一篇    下一篇

胰岛素通过mTORC2/SGK1途径上调肺泡上皮钠通道α亚基的作用机制

何婧, 戚迪, 王导新   

  1. 重庆医科大学附属第二医院呼吸与危重症医学科, 重庆 400010
  • 收稿日期:2014-10-20 发布日期:2015-08-01
  • 通讯作者: 王导新,教授,主任医师,博士研究生导师(Tel:023-63693094,E-mail:wangdaoxin1@163.com) E-mail:wangdaoxin1@163.com
  • 作者简介:何婧(1987-),女,重庆市人,住院医师,在读医学博士,主要从事呼吸危重症基础与临床方面的研究。
  • 基金资助:

    国家自然科学基金资助课题(81270141)

Mechanism of insulin in up-regulating epithelial sodium channel α-subunit via mTORC2/SGK1 signaling pathway

HE Jing, QI Di, WANG Daoxin   

  1. Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
  • Received:2014-10-20 Published:2015-08-01

摘要:

目的: 研究mTORC2/SGK1在胰岛素上调肺泡上皮钠通道α亚基(α-ENaC)中的作用,阐明胰岛素促进小鼠急性肺损伤(ALI)时肺水肿清除的机制。方法: C57BL/6J小鼠随机分为对照组、脂多糖(LPS)组、胰岛素组、PP242(mTORC1/2抑制剂)组和雷帕霉素(特异性mTORC1抑制剂)组,每组10只。经相应处理后分别留取标本检测小鼠肺湿/干质量比(W/D)、肺泡液体清除率(AFC),HE染色观察肺组织病理学变化,Western blotting法检测肺组织中α-ENaC表达水平及pSGK1(Ser422)磷酸化水平。结果: 与LPS组比较,胰岛素组小鼠肺组织病理评分、肺W/D明显降低(P<0.05),AFC明显增加(P<0.05)。与对照组比较,LPS组小鼠肺组织中α-ENaC蛋白表达水平明显降低(P<0.05);与LPS组比较,胰岛素组小鼠肺组织中α-ENaC蛋白表达水平和pSGK1(Ser422)磷酸化水平明显升高(P<0.05);与胰岛素组比较,PP242组小鼠肺组织中α-ENaC蛋白表达和pSGK1(Ser422)磷酸化水平明显降低(P<0.05)。结论: 胰岛素通过mTORC2途径激活SGK1,上调α-ENaC表达,促进肺泡液体清除,对ALI/急性呼吸窘迫综合征(ARDS)的预后有一定的改善作用。

关键词: 急性肺损伤, 急性呼吸窘迫综合征, 胰岛素, 血清糖皮质激素诱导激酶1, 上皮钠通道, 哺乳动物雷帕霉素靶蛋白复合物

Abstract:

Objective To study the role of mTORC2/SGK1 signaling pathway in the up-regulation of alveolar epithelial sodium channel α-subunit (α-ENaC) by insulin,and to clarify the mechanism of insulin in promoting the lung edema clearance in the acute lung injury(ALI) mice. Methods The C57BL/6J mice were randomly divided into control group,LPS group,insulin group (LPS+insulin),PP242 group (PP242+LPS+insulin) and rapamycin group (rapamycin+LPS+insulin),with 10 mice in each group. The lung wet/dry weight(W/D) ratios and alveolar fluid clearance(AFC) of the mice were detected. HE staining was used to observe the pathological changes of lung tissue. The protein expression levels of α-ENaC and phosphorylated serum-and the levels of glucocorticoid-inducible kinase 1 (SGK1) at Ser422 in lung tissue were determined by Western blotting method. Results Compared with LPS group, the lung injury score and W/D ratio in insulin group were decreased significantly (P<0.05) and the AFC was increased significantly (P<0.05).The expression level of α-ENaC protein in LPS group was decreased significantly compared with control group (P<0.05). The expression levels of both α-ENaC protein and pSGK1(Ser422) in insulin group were significantly increased compared with LPS group (P<0.05).Compared with insulin group,the α-ENaC protein expression level and phosphorylated SGK1(Ser422) levelin PP242 group were decreased(P<0.05). Conclusion Through mTORC2 pathway,insulin activates the SGK1 and up-regulates the expression of α-ENaC protein to accelerate the AFC,which is beneficial to the prognosis of ALI/acute respiratory distress syndrome(ARDS).

Key words: acute lung injury, acute respiratory distress syndrome, insulin, serum-and glucocorticoid-inducible kinase 1, epithelial sodium channel, mammalian target of rapamycin complex

中图分类号: 

  • R563.8