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Mass spectrometry based lipidomics to study lipid effects of naphthalene in the mouse serum
|Publication Year :||2020|
第二部分則應用優化後的分析平台對萘暴露小鼠血清中的脂質體進行篩查。使用七週大的雄性ICR小鼠，分成對照組、低劑量與高劑量暴露組，分別以腹腔注射施予以橄欖油為載體、劑量為0、100、200 mg/kg body weight的萘。小鼠於暴露後24小時犧牲，抽取血清樣品並萃取脂質後上機分析。偏最小平方判別法結果顯示三組間有明顯的分群。磷脂醯膽鹼在萘引起的小鼠血清顯著改變脂質中所占比例最高；而改變幅度最大的則是磷脂醯絲氨酸。此外，本研究也觀察到包含磷脂醯乙醇胺、神經醯胺、三酸甘油脂在內等多種脂質擾動，變動方向與幅度依據之質類別不盡相同，並可能與萘所造成的傷害或生物體對發炎反應的調控相關。
Naphthalene, an air pollutant widely present in the environment, came from various forms of incomplete combustion, such as second-hand smoke, traffic exhaust and factory emissions. Toxicity induced by naphthalene is species- and organ-specific. Literatures pointed out that acute exposure to naphthalene caused respiratory toxicity in mice, especially swelling, vacuolation, and necrosis of Clara cells in mouse lungs with dose-response effects. Lipids are the main components of cell membranes, and also participating in various physiological functions. Previously, our group had also observed naphthalene-induced perturbation of phosphocholine-containing lipids in the mouse lungs and bronchoalveolar lavage fluid. Ultra-high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer based lipidomics was applied in this study to examine serum from mice treated with different doses of naphthalene. We aim to profile the perturbation of more lipid classes to understand the molecular events of naphthalene.
The first part of present study tested the instrumental conditions such as column length, temperature, gradient settings, and mass spectrum acquisition rate to optimize the analysis platform currently used in our group. We successfully shortened the analysis time while maintaining a large feature amount. Lipid standard performance showed that this system could effectively detect various lipids such as glycerolipids, glycerophospholipids, and sphingolipids. More than 90% of features showed the coefficient of variation less than 20%, indicating well-stability in the system.
In the second part, the optimized analytical platform was applied to profile the lipids in the serum of naphthalene-treated mice. 7-week-old male ICR mice were divided into control group, low-dose, and high-dose exposure group. 0, 100, and 200 mg/kg body weight of naphthalene was treated with olive oil as a carrier by intraperitoneal injection. Mice were sacrificed 24 hours after exposure and serum samples were taken for lipid extraction and analysis. The score plot of partial least squares discriminant analysis showed that three groups separated clearly. Glycerophosphocholines accounted for the highest proportion of naphthalene induced significantly changed lipids in mouse serum; and the most dramatic changed lipids were glycerophosphoserines. Meanwhile, the disturbances of various lipid classes including glycerophosphoethanolamines, ceramides, and triacylglycerols were observed. These disturbances might be related to the naphthalene induced damage or the organism's regulation of the inflammatory responses.
This optimized analytical platform can be applied to investigate the lipid composition and changes in different organs or biological fluids in the future. Present study profiled a wide range of lipid classes in naphthalene-treated mouse serum to provide a more comprehensive understanding of naphthalene induced lipid effects. These results may help us further explore the possible toxicity mechanisms of naphthalene, and also provide knowledge for biomarker development.
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