基于脂质组学的脱氢蟾蜍色胺对脂多糖介导斑马鱼胚胎的抗炎机制研究

Study on the anti-inflammatory mechanism of dehydrobufotenine on LPS-mediated zebrafish model based on lipidomics

目的:基于脂质组学技术阐明脱氢蟾蜍色胺对脂多糖(LPS)介导的炎症斑马鱼模型的抗炎机制。方法:利用LPS刺激转基因荧光斑马鱼,建立炎症模型,以脱氢蟾蜍色胺进行干预给药,基于超高效液相串联质谱(UPLC-QE-MS)技术对各样品组进行代谢轮廓分析,利用多元统计分析筛选差异代谢物。结果:LPS刺激后,卵黄囊中性粒细胞数显著性升高(P<0.01),说明造模成功,脱氢蟾蜍色胺给药后,中性粒细胞数显著性降低,抗炎率最高达58%;根据多元统计分析从模型组与空白组筛出19个脂质差异代谢物,其中包括16个甘油三酯,2个鞘磷脂,1个神经酰胺。结论:蟾皮中脱氢蟾蜍色胺对LPS介导的斑马鱼炎症模型有明显抗炎活性,可能通过调节甘油三酯和鞘脂等脂质的稳态来发挥抗炎作用。

Objective: To clarify the anti-inflammatory mechanism of dehydrobufotenine on LPS-mediated zebrafish model based on lipidomics. Methods: LPS was used to stimulate the transgenic zebrafish to establish an inflammatory model, and dehydrobufotenine was used to intervene. Based on UPLC-QE-MS technology, metabolic profiling analysis was performed for each group, and potential lipid metabolites were screened out by multivariate statistical analysis. Results: After LPS stimulation, the number of neutrophils in yolk was significantly increased(P<0.01), indicating successful modeling. After administration of dehydrobufotenine, the number of neutrophils decreased significantly, and the anti-inflammatory rate reached 58%. According to the multivariate statistical analysis, 19 lipid biomarkers, including 16 triglycerides, 2 sphingomyelins and 1 ceramide were screened. Conclusion: Dehydrobufotenine may exert an anti-inflammatory effect by regulating lipid homeostasis such as triglycerides and sphingolipids in LPS-mediated zebrafish model.