氯代多氟醚基磺酸对稀有鮈鲫肝脏组织损伤及其毒理学机制研究

Liver Tissue Damage and Toxicological Mechanism of F-53B on Chinese Rare Minnow(Gobiocypris Rarus)

6:2氯代多氟醚基磺酸(F-53B)作为全氟辛烷磺酸(perfluorooctane sulfonate,PFOS)的替代品,已在金属电镀行业使用了40多年,这种普遍使用导致其在环境、野生动物和人体中广泛检出,且有研究表明F-53B具有肝细胞毒性作用,但其脂毒性机制尚不明确。将5月龄稀有鮈鲫暴露于0、10和200μg·L^(-1)28 d,以蛋白质组学作为研究手段,探究F-53B对稀有鮈鲫肝脏的脂毒性效应机制。在28 d暴露后,200μg·L^(-1)处理组观察到明显的血脂异常,肝脏蛋白组分析表明与脂质代谢相关的途径受到显著影响,与对照组相比,其中10μg·L^(-1)组与脂质代谢相关的上调蛋白有19个,下调的有4个,200μg·L^(-1)组上调蛋白有15个,下调蛋白9个,共同上调蛋白12个,下调蛋白2个,涉及脂肪酸降解、脂肪酸氧化、转运途径中酶的上调。同时PPAR信号通路参与了F-53B诱导的脂质代谢紊乱,表现为对PPAR的3种亚型的蛋白表达均产生激活作用,导致成骨/成脂分化失衡。这表明F-53B可破坏PPAR信号通路,破坏稀有鮈鲫的脂质稳态,结果可为F-53B脂毒作用机制研究提供新的思路。

As a substitute for perfluorooctane sulfonic acid(PFOS)commonly used in the Chinese market,6:2 chlorinated polyfluoroalkyl ether sulfonic acid(F-53B)has been used in the metal plating industry for over 40 years.It has been widely detected in the environment,wildlife and humans.Some studies have shown that F-53B has hepatocytotoxic effects,but the mechanism of its lipotoxicity has been less studied.We exposed the 5-month-old Chinese rare minnow to 0,10,and 200μg·L^(-1)F-53B for 28 d.Proteomics was used as a research tool to study the mechanism of lipotoxic effect of F-53B on the liver of Chinese rare minnow.Obvious dyslipidemia was observed after 28 d exposure,in the 200μg·L^(-1)F-53B-treated group.Liver proteomic analyses revealed that pathways associated with lipid metabolism were significantly affected,with 19 up-regulated and 4 down-regulated proteins associated with lipid metabolism in the 10μg·L^(-1)F-53B-treated group,15 up-regulated and 9 down-regulated proteins in the 200μg·L^(-1)F-53B-treated group,and 12 co-regulated proteins up-regulated and 2 down-regulated proteins in the 200μg·L^(-1)group,as compared with the control group.The up-regulation of enzymes in fatty acid degradation,fatty acid oxidation,and fatty acid transport pathways were involved.At the same time the PPAR signaling pathway was involved in F-53B-induced lipid metabolism disorders,as evidenced by activation of proteins expression of all three isoforms of PPAR,leading to an imbalance in osteogenic/lipogenic differentiation.It was shown that F-53B could affect the PPAR signaling pathway and disrupt the lipid homeostasis of Chinese rare minnow,and the results could provide new insights for the study of the lipotoxic action mechanism of F-53B.