塑料添加剂暴露诱导的炎症性脂质和脂肪酸代谢异常在儿童哮喘中的作用
2024/02/23
背景:脂质代谢在哮喘的发生、发展中起重要作用,邻苯二甲酸酯(PAEs)和有机磷阻燃剂(OPFRs)可干扰脂质代谢。作为一种慢性炎症性呼吸系统疾病,PAEs和OPFRs暴露可增加儿童哮喘的发生风险,但PAEs和OPFRs在哮喘发病和进展中的作用机制尚不完全清楚。
方法:我们通过液相色谱-质谱联用分析了PAEs和OPFRs同源物的血清水平,以及其与哮喘,支气管炎(急性炎症)和健康(非炎症)儿童脂质代谢失调的关系。
结果:深圳市1-5岁儿童血清中检出8种PAEs和9种OPFRs同源物,总中位数分别为615.16 ng/mL和17.06 ng/mL。此外,哮喘组患儿血清中邻苯二甲酸单甲基酯(MMP)、磷酸三丙酯(TPP)和磷酸三正丁基酯(TNBP)水平显著高于健康对照组和支气管炎对照组。基于血清脂质组数据,通过机器学习随机森林模型筛选出31种哮喘特征脂质和脂肪酸,其中棕榈酸、12,13-DiHODE、14,21-DiHDHA、前列腺素D2和LysoPA(18:2)等炎症特征脂质和脂肪酸的改变与血清高水平MMP、TPP和TNBP显著相关。
结论:这些结果提示PAEs和OPFRs通过破坏炎症性脂质和脂肪酸代谢促进儿童哮喘的发生,为更好地理解塑料添加剂对儿童哮喘的影响提供了新的视角。
Role of inflammatory lipid and fatty acid metabolic abnormalities induced by plastic additives exposure in childhood asthma
Z. Y. Chen, F. Li, L. Fu, Y. Xia, Y. Luo, A. Guo, et al.
Abstract
BACKGROUND:Lipid metabolism play an essential role in occurrence and development of asthma, and it can be disturbed by phthalate esters (PAEs) and organophosphate flame retardants (OPFRs). As a chronic inflammatory respiratory disease, the occurrence risk of childhood asthma is increased by PAEs and OPFRs exposure, but it remains not entirely clear how PAEs and OPFRs contribute the onset and progress of the disease.
METHODS:We have profiled the serum levels of PAEs and OPFRs congeners by liquid chromatography coupled with mass spectrometry, and its relationships with the dysregulation of lipid metabolism in asthmatic, bronchitic (acute inflammation) and healthy (non-inflammation) children.
RESULTS:Eight PAEs and nine OPFRs congeners were found in the serum of children (1-5 years old) from Shenzhen, and their total median levels were 615.16 ng/mL and 17.06 ng/mL, respectively. Moreover, the serum levels of mono-methyl phthalate (MMP), tri-propyl phosphate (TPP) and tri-n-butyl phosphate (TNBP) were significant higher in asthmatic children than in healthy and bronchitic children as control. Thirty-one characteristic lipids and fatty acids of asthma were screened by machine-learning random forest model based on serum lipidome data, and the alterations of inflammatory characteristic lipids and fatty acids including palmitic acids, 12,13-DiHODE, 14,21-DiHDHA, prostaglandin D2 and LysoPA (18:2) showed significant correlated with high serum levels of MMP, TPP and TNBP.
CONCLUSIONS: These results imply PAEs and OPFRs promote the occurrence of childhood asthma via disrupting inflammatory lipid and fatty acid metabolism, and provide a novel sight for better understanding the effects of plastic additives on childhood asthma.
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