文章摘要
郭 媛,孙大燕,李 轶,郝 萌,王久存.1-磷酸鞘氨醇改善缺氧诱导的肺上皮细胞损伤[J].,2022,(1):1-5
1-磷酸鞘氨醇改善缺氧诱导的肺上皮细胞损伤
Protective Effect of Sphingominol 1-phosphate for Hypoxia-induced Lung Epithelial Cells Injury
投稿时间:2021-05-30  修订日期:2021-06-27
DOI:10.13241/j.cnki.pmb.2022.01.001
中文关键词: 1-磷酸鞘氨醇  低氧暴露  肺上皮细胞  线粒体  氧化损伤
英文关键词: S1P  Hypoxia  Lung epithelial cells  Mitochondrion  Oxidative Stress
基金项目:上海市科技重大专项 (2017SHZDZX01)
作者单位E-mail
郭 媛 复旦大学人类表型组研究院 上海 201203 18210700113@fudan.com 
孙大燕 复旦大学人类表型组研究院 上海 201203  
李 轶 复旦大学人类表型组研究院 上海 201203  
郝 萌 复旦大学人类表型组研究院 上海 201203  
王久存 复旦大学人类表型组研究院 上海 201203  
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中文摘要:
      摘要 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1 μM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。
英文摘要:
      ABSTRACT Objective: How to reduce the lung ingury caused by hypoxia is a challenge when people enter the high altitude. The purpose of this study is to explore the protective effect of exogenous sphingosinol 1-phosphate (S1P) on lung epithelial cells during hypoxic exposure. Methods: BEAS 2B cells were pretreated with S1P at different concentrations for 4 hours and then placed in a hypoxia incubator (1% oxygen concentration) to simulate hypoxia exposure during 24 h and 48 h, and then detect the proliferative activity,early apoptosis and mitochondria-related functions; in addition, the expression level of the receptor genes(S1PR1-3) were tested by real-time qPCR. Results: Exogenous S1P preconditioning can increase the expression level of S1PR3 significantly in BEAS 2B; During 24 h - 48 h of hypoxia exposure, S1P pretreatment at 1 μM had a significant protective effect on BEAS 2B, especially improving Mitochondrial Membrane 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 S1P preconditioning can protect lung epithelial cells by inhibition of hypoxia-induced oxidative stress injury. S1P has important application value in preventing altitude sickness.
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