环境浓度微塑料增强TDCIPP肝脏毒性及其分子响应机制

Promotion Effects and Molecular Response Mechanism of Polyamide Microplastics on Hepatotoxicity of TDCIPP at Environmental Concentration

微塑料的生态环境及健康风险日益引起关注。为阐明微塑料对共存污染物毒性效应的影响,实验以斑马鱼为模式生物,探究环境相关浓度聚酰胺(PA;100μg·L^(-1))微塑料与磷酸三(1,3-二氯异丙基)酯(TDCIPP;0.4、2和10μg·L^(-1))复合暴露4个月对斑马鱼肝脏结构和功能的影响,并揭示其分子响应机制。结果显示,100μg·L^(-1)的PA处理对斑马鱼无明显不良影响,相比于10μg·L^(-1) TDCIPP处理组,PA共暴露使斑马鱼体长、体质量和肝体指数分别降低5.9%、11.7%、12.8%;单独TDCIPP处理组和PA与TDCIPP复合处理组肝脏内TDCIPP含量分别为0.18~4.12μg·g^(-1)和0.32~5.30μg·g^(-1)(以单位湿质量计),表明PA可显著提高TDCIPP在斑马鱼肝脏内的富集含量;相比于空白和单一处理组,PA和TDCIPP复合胁迫下肝脏活性氧、抗氧化酶活性、炎症因子水平显著升高,肝细胞核萎缩、胞质溶解和组织坏死等现象加剧。代谢组学分析发现,单一PA或TDCIPP主要干扰肝脏糖类有氧代谢和三羧酸循环,复合暴露时肝脏ATP合成抑制进一步加剧,解毒和排泄功能相关的谷胱甘肽合成和精氨酸代谢过程显著下调,具有抗炎效应的不饱和脂肪酸合成过程上调。上述结果从酶活、炎症效应、组织损伤及内源代谢方面阐明环境浓度PA微塑料增强TDCIPP肝脏毒性的机制。

The ecological environment and health risks of microplastics are of increasing concern.Herein,this study investigated the effects of environmentally relevant concentrations of polyamide(PA;100μg·L^(-1))microplastics combined with tris(1,3-dichloro-2-propyl)phosphate(TDCIPP;0.4,2,and 10μg·L^(-1))on the structure and function of zebrafish liver after 4 months of co-exposure and the molecular mechanisms were revealed,aiming to elucidate the role of microplastics toward the toxic effects of co-existing pollutants.The results indicated that PA alone exhibited no significant negative effects on zebrafish.Compared with the individual TDCIPP(10μg·L^(-1))group,the body length,body weight and hepatosomatic index of zebrafish in the PA co-exposed group decreased by 5.9%,11.7%,and 12.8%,respectively.The TDCIPP contents in liver from individual TDCIPP and PA+TDCIPP groups reached 0.18~4.12μg·g^(-1) and 0.32~5.30μg·g^(-1)(wet weight),respectively,signifying that PA significantly increased the TDCIPP enrichment in the liver.The levels of reactive oxygen species,antioxidant enzyme activities,and inflammatory factors in the liver from the PA and TDCIPP co-exposure groups were obviously up-regulated relative to those individual groups,and the hepatocyte nuclear atrophy,cytosolysis and tissue necrosis were aggravated.Metabolomic assays revealed that single PA or TDCIPP mainly interfered with hepatic carbohydrate aerobic metabolism and tricarboxylic acid cycle,and the inhibition on hepatic ATP biosynthesis was further exacerbated upon co-exposure to PA and TDCIPP.Glutathione synthesis and arginine metabolism pathways involved in liver detoxification and pollutant excretion were down-regulated and the biosynthesis of unsaturated fatty acids with anti-inflammatory function was up-regulated.The above findings elucidated the mechanisms by which environmentally relevant concentrations of PA microplastics elevate the hepatotoxicity of TDCIPP in terms of enzyme activity,inflammation,tissue injury,and endogenous metabolism.