胚胎期和哺乳早期全氟辛烷磺酸盐(PFOS)暴露对大鼠肝脏脂肪酸代谢影响的microRNA组学研究

研究低剂量全氟辛烷磺酸(perfluorooctane sulfonate,PFOS)对大鼠幼仔肝脏中microRNA的表达及脂肪酸代谢的影响,并且从microRNA分子角度探讨PFOS对肝脏相关功能影响的分子毒性机制及预测其他一些潜在的毒性效应。PFOS染毒剂量为3.2mg·kg-1,对照组给予同等体积的含2%的聚氧乙烯山梨糖醇酐单月桂酸酯乳化剂(Tween 20),利用高通量miRNA芯片技术观察了胚胎期和哺乳早期经PFOS染毒后出生第1和7天(PND1和PND7)大鼠肝脏组织miRNA的表达情况。结果显示,PFOS能够引起仔鼠肝脏microRNA表达量的变化,PND1和PND7时显著变化的microRNA个数分别为46和9个。miR-125a-3p、miR-23a*、miR-25及miR-494同时在PND1和PND7显著性表达,PND1呈现下调性变化,PND7呈现上调性变化。通过生物信息学和统计学分析发现:PFOS具有大鼠肝脏早期发育毒性,而且胚胎期的毒性效应强于哺乳早期;大鼠幼仔肝脏早期发育中,PFOS对其糖脂代谢及细胞凋亡过程具有毒性效应;胚胎期和哺乳早期,在低剂量PFOS暴露下,β和ω氧化代谢是肝脏脂肪酸代谢的主要方式;脂酰COA合成酶、脂酰COA脱氢酶及烯酰COA水合酶等脂肪酸代谢过程的关键酶,是PFOS暴露下microRNA潜在的靶分子。研究表明,PFOS具有多种肝脏早期发育毒性,低剂量PFOS暴露下,microRNA能够调节肝脏脂肪酸代谢相关靶基因的表达,进而调控脂肪酸代谢过程。

Effects of Perfluorooctane Sulfonate (PFOS) Exposure on Rat Liver Fatty Acid Metabolism During Embryonic Period and Early Lactation at MicroRNA Level

The study is aimed to investigate the effects of low-dose exposure of PFOS on microRNA expression pattern and fatty acid metabolism in neonatal rat livers,and reveal the molecular mechanisms of PFOS toxicity to liver functions from the angle of microRNA molecules,then predict other related potential toxic effects.MicroRNA arrays were used to profile the expression of liver microRNA in neonatal rats on postnatal day(PND) 1 and 7,which were exposed to 3.2 mg kg-1 PFOS at prenatal and neonatal stages,with the control group fed with polyethylene glycol sorbitan monolaurate(Tween 20).Results showed that PFOS exposure induced significant alteration in the expression of 46 and 9 microRNA in liver of rats on PND 1 and PND 7,respectively.MiR-125a-3p,miR-23a*,miR-25 and miR-494 showed significantly downregulated changes on PND1 and upregulated changes on PND7,respectively.The results of bioinformatics and statistics analysis showed that that in PFOS could induce early developmental toxicity to rat livers,which was more significant in embryonic period than that in early lactation.In addition,low-dose PFOS exposure at prenatal and neonatal stages,β and ω oxidative pathways may involve in fatty acid metabolic processes.Acyl COA synthetic enzyme,acyl COA dehydrogenase and enoyl COA hydrated enzyme as the key enzymes of the fatty acid metabolic processes were potential target molecules of microRNA with PFOS exposure.It is indicated that PFOS showed liver early developmental multi-toxicities PFOS exposure at low doses may regulate the expressions of the potential target genes related to fatty acid metabolism by microRNA.