麻痹性贝毒亚慢性暴露对小鼠肝脏脂质代谢的影响

Effects of sub-chronic exposure to paralytic shellfish toxins on liver lipidomics in mice

中文关键词:  麻痹性贝毒  脂质组学  差异脂质  代谢通路

英文关键词:paralytic shellfish toxins  lipidomics  differential lipids  metabolic pathways

中文摘要:

      目的 评估亚慢性剂量麻痹性贝毒(paralytic shell?sh toxins, PSTs)对小鼠肝脏的影响。方法 本研究通过口服灌胃的方式, 采用的脂质组学技术评估不同剂量浓度PSTs对肝脏脂质代谢组学的影响。结果 高中剂量组(大于100 μg STXeq/kg BW)暴露导致脂质代谢异常, 其中甘油磷脂类(glycerophospholipids, GP)为主要差异脂质代谢物, 磷脂酰乙醇胺(18:3/22:6) [phosphatidylethanolamine (18:3/22:6), PE (18:3/22:6)]、PE (16:0/18:0)、16(17)-环氧二十二碳五烯酸的相对含量降低, 而溶血磷脂酰乙醇胺(P-16:0/0:0)的相对含量升高, 这些脂质可作为PSTs暴露导致肝脏损伤的生物标志物。相比之下, 低剂量组(45 μg STXeq/kg BW)未对小鼠肝脏脂质造成显著性影响。差异脂质的代谢途径富集分析表明, α-亚麻酸代谢、甘油酯代谢、花生四烯酸代谢和类固醇激素的生物合成共同参与了3个PSTs实验组的脂质代谢。结论 PSTs对小鼠肝脏脂质代谢的影响具有剂量依赖性特征, 脂质功能障碍可能影响PSTs的神经毒性作用, 本研究为探索PSTs对小鼠肝脏损伤机制提供了理论参考。

英文摘要:

      Objective To evaluate the effects of sub-chronic doses of paralytic shell?sh toxins (PSTs) on the livers of mice. Methods In the present study, the effects of different dose concentrations PSTs on hepatic lipid metabolomics were assessed by oral gavage using the lipidomics technique. Results Exposure to the high-and medium-dose group (greater than 100 μg STXeq/kg BW) resulted in abnormal lipid metabolism, with glycerophospholipids (GP) as the major differential lipid metabolites, phosphatidylethanolamine (18:3/22:6) [PE (18:3/22:6)], PE (16:0/18:0), and 16(17)-epoxydocosapentaenoic acid were lower, whereas the relative content of lysophosphatidylethanolamine (P-16:0/0:0) was elevated in relative levels of these lipids, which might serve as biomarkers of liver injury due to PSTs exposure. In contrast, the low dose group (45 μg STXeq/kg BW) did not significantly affect mouse liver lipids. Metabolic pathway enrichment analysis of differential lipids showed that α-linolenic acid metabolism, glyceride metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis were collectively involved in lipid metabolism in the 3 kinds of PSTs experimental groups. Conclusion The effects of PSTs on hepatic lipid metabolism in mice are characterized by a dose-dependent pattern, and lipid dysfunction may affect the neurotoxic effects of PSTs. This study provides a theoretical reference for exploring the mechanism of hepatic injury by PSTs in mice.