胰岛素通过PI3K/AKT及PI3K/ERK通路减轻脂多糖对钠泵α1亚基的抑制  

Insulin attenuates the inhibition effect of lipopolysaccharide on Na^+-K^+-ATPase α1 via PI3K/AKT and PI3K/ERK pathway

作　　者：刘焕淼 陈焯辉 吴迪 黄雪婷 万齐全[1] LIU Huanmiao;CHEN Zhuohui;WU Di;HUANG Xueting;WAN Qiquan(Department of Transplant Surgery,the Third Xiangya Hospital,Central South University,Changsha 410013,Hunan,China;Xiangya School of Medicine,Central South University,Changsha 410083,Hunan,China)

机构地区：[1]中南大学湘雅三医院移植中心监护室,湖南长沙410013 [2]中南大学湘雅医学院,湖南长沙410083

出　　处：《中国临床药理学与治疗学》2019年第8期896-902,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:研究胰岛素减轻脂多糖对肺泡Ⅱ型上皮细胞Na^+-K^+-ATPaseα1亚基表达抑制的分子机制。方法:以A549细胞为研究对象,脂多糖(1μg/mL)诱导8h后,再加用胰岛素(100 nmol/L)处理4 h,采用Western blot法检测Na^+-K^+-ATPaseα1亚基表达及AKT、ERK1/2、p70s6k、NEDD4-2总蛋白表达及其磷酸化水平变化。结果:A549细胞在1μg/mL脂多糖作用下,Na^+-K^+-ATPaseα1亚基蛋白表达显著降低。胰岛素处理可部分解除脂多糖对A549细胞Na^+-K^+-ATPaseα1亚基表达的抑制。胰岛素上调Na^+-K^+-ATPaseα1亚基表达是通过改变PI3K/AKT及PI3K/ERK通路中关键蛋白AKT、NEDD4-2、ERK1/2、p70s6k的磷酸化水平来实现的。结论:胰岛素通过调控PI3K/AKT及PI3K/ERK通路部分解除脂多糖对肺泡II型上皮细胞Na^+-K^+-ATPaseα1亚基表达的抑制,这为临床上采用胰岛素干预急性呼吸窘迫综合征提供了初步实验依据。AIM:To investigate the molecular mechanism of insulin alleviating the inhibition of lipopolysaccharide on the expression of Na^+-K^+-ATPaseα1 subunit in pulmonary alveoli type II alveolar cells.METHODS:A549 cells,firstly induced by lipopolysaccharide(1μg/mL)for 8 hours,were used as the research objects,then treated with insulin(100 nmol/L)for 4 hours.Western blot was used to detect the expression ofNa^+-K^+-ATPaseα1 subunit and AKT,ERK1/2,p70s6k,NEDD4-2 total protein expression and changes in their phosphorylation levels.RESULTS:The expression of Na^+-K^+-ATPaseα1 subunit protein was significantly decreased in A549 cells when treated with 1μg/mL lipopolysaccharide.Insulin treatment could partially relieve the lipopolysaccharide inhibition on the expression of Na^+-K^+-ATPaseα1 subunit in A549 cells.Insulin up-regulation of Na^+-K^+-ATPaseα1 subunit expression was achieved by altering the phosphorylation levels of the key proteins AKT,NEDD4-2,ERK1/2,and p70s6k in the PI3K/AKT and PI3K/ERK pathways.CONCLUSION:Insulin could partially relieve the lipopolysaccharide inhibition on the expression of Na^+-K^+-ATPaseα1 subunit in pulmonary alveoli type II alveolar cells by regulating the PI3K/AKT and PI3K/ERK pathways,which provided a preliminary experimental basis for the clinical use of insulin to intervene in acute respiratory distress syndrome.

关 键 词：胰岛素 脂多糖 急性呼吸窘迫综合征 Na^+-K^+-ATPaseα1 PI3K通路 

分 类 号：R965.2[医药卫生—药理学]