1-磷酸鞘氨醇改善缺氧诱导的肺上皮细胞损伤

目的:如何减轻缺氧造成的肺损伤是平原人群进入高原环境时面临的难题。本研究旨在探索外源性1-磷酸鞘氨醇(S1P)对低氧暴露诱导肺上皮细胞损伤的改善作用。方法:对肺上皮细胞(BEAS 2B细胞)进行4 h不同浓度的S1P预处理,之后放入低氧培养箱(氧气浓度为1%)模拟24 h和48 h的低氧暴露,检测细胞的增殖活性、早期凋亡以及线粒体相关功能;通过实时荧光定量PCR检测受体基因(S1PR1-3)的表达水平。结果:外源性S1P预处理可在BEAS 2B细胞中显著提高S1PR3的表达水平;对于24 h-48 h的急性低氧暴露,给予1μM浓度的S1P预处理时对细胞具有显著的保护作用,主要表现在线粒体功能改善、细胞增殖活性提升及早期凋亡率下降,包括:线粒体膜电位(MMP)和三磷酸腺苷(ATP)水平显著升高(P<0.0005),线粒体活性氧(ROS)产生显著减少(P<0.0001),从而显著提高了细胞的增殖活性(P<0.005),并降低早期凋亡率。结论:外源性S1P预处理能通过改善低氧诱导的氧化应激损伤保护肺上皮细胞。S1P在预防急性高原病、改善高原反应方面具有潜在应用价值。

Protective Effect of Sphingominol 1-phosphate for Hypoxia-induced Lung Epithelial Cells Injury

Objective How to reduce the lung ingury caused by hypoxia is a challenge when people enter the high altitude.Thepurpose of this study is to explore the protective effect of exogenous sphingosinol 1-phosphate(S1P)on lung epithelial cells duringhypoxic exposure.Methods:BEAS 2B cells were pretreated with S1P at different concentrations for 4 hours and then placed in a hypoxiaincubator(1%oxygen concentration)to simulate hypoxia exposure during 24 h and 48 h,and then detect the proliferative activity,earlyapoptosis and mitochondria-related functions;in addition,the expression level of the receptor genes(S1PR1-3)were tested by real-timeqPCR.Results:Exogenous S1P preconditioning can increase the expression level of S1PR3 significantly in BEAS 2B;During 24 h-48 hof hypoxia exposure,S1P pretreatment at 1μM had a significant protective effect on BEAS 2B,especially improving MitochondrialMembrane Potential(MMP)and Adenosine Triphosphate(ATP)levels(P<0.0005),reducing Reactive Oxygen Species(ROS)production(P<0.0001),Thus,increase the proliferation activity(P<0.005)and reduce the early apoptosis rate of cells.Conclusion Exogenous S1Ppreconditioning can protect lung epithelial cells by inhibition of hypoxia-induced oxidative stress injury.S1P has important applicationvalue in preventing altitude sickness.