纳米聚苯乙烯长期暴露中小鼠代谢谱的动态变化

Dynamic changes of metabolic profile in mice exposed to polystyrene nanoparticles

目的基于代谢组学的方法,揭示纳米塑料长期暴露对机体代谢的动态影响。方法13月龄的C57BL/6J雄鼠以0、1、10 mg/kg剂量的纳米聚苯乙烯(polystyrene nanoparticles,PS-NPs)进行灌胃,灌胃暴露时长为9个月。分别于暴露第1、3、6、9个月,处死部分小鼠并收集其血液。最后采用TM广靶代谢组学技术对血清差异代谢物进行分析。结果同剂量组内不同暴露时间节点(暴露第1、3、6、9个月)的样本点均能明显分离,发现尿胆素含量随暴露时长的增加而减少,并与卟啉与叶绿素代谢通路密切相关。在长期暴露结束后(暴露第9个月),在对照组与不同暴露剂量组间比较中共发现135个差异代谢物。其中50个代谢物含量上调,85个代谢物含量下调。聚类分析发现,花生四烯酸代谢和嘌呤代谢通路是主要的受干扰通路,与该通路相关的差异代谢物含量(2,3-dinor-8异前列腺素F2α、黄嘌呤、2-脱氧肌苷、腺苷-3′-磷酸、次黄嘌呤等)均明显上调。结论小鼠在长期的PS-NPs暴露过程(中年-老年)中,其血清代谢谱发生改变。其中,尿胆素与PS-NPs暴露时长相关,是潜在的敏感标志物。2,3-dinor-8异前列腺素F2α、黄嘌呤等是潜在的特异性标志物,这些代谢物提示花生四烯酸代谢和嘌呤代谢通路是研究PS-NPs暴露损伤的可能机制通路。

Objective To exposure the dynamic effects of nano-plastics on the body′s metabolism during long-term exposure based on the method of metabolomics.Methods Male C57BL/6J mice,aged 13 months,were exposed to polystyrene nanoparticles(PS-NPs)at doses of 0,1 and 10 mg/kg over a period of 9 months via gastric lavage.After one,three,six,and nine months intervals post-exposure,random selected mice from each group were killed and their blood samples collected.Subsequently,the technique of TM wide-target metabolomics was utilized for the classification of serum differential metabolites.Results The sample points of different exposure time nodes(first,third,sixth,and ninth months)within the same dose group were distinguishable.It was discovered that the urobilin content decreased as exposure time increased and was closely related to the metabolic pathways of porphyrin and chlorophyll.After long-term exposure(nine months),135 distinct metabolites were identified in the comparison between the control group and groups with varying exposure doses.Out of these,50 metabolites were upregulated and 85 metabolites were downregulated.Cluster analysis revealed that arachidonic acid metabolism and purine metabolism pathway were the most perturbed.The contents of differential metabolites associated with these pathways(e.g.,2,3-dinor-8-iso Prostaglandin F2α,Xanthine,2′-Deoxyinosine,3′-Aenylic Acid,Hypoxanthine)were markedly upregulated.Conclusions The serum metabolic profile of mice changed exposed to PS-NPs for extended exposure was altered(from middle age to old age).Among the altered differential metabolites,urobilin is linked to the duration of PS-NPs exposure and is a potential sensitive marker.In addition,2,3-dinor-8-iso Prostaglandin F2αand Xanthine are potential specific markers.These metabolites suggest the pathways for the metabolism of arachidonic acid and purines are potential mechanisms for studying PS-NPs exposure damage.