双酚A及其3种替代物对肝细胞甘油三酯合成的影响

Effects of bisphenol A and its three analogs on triglyceride synthesis in hepatocytes

目的探讨双酚A(BPA)及其替代物双酚AF(BPAF)、双酚B(BPB)、双酚S(BPS)是否可引起肝细胞脂质蓄积。方法BPA、BPAF、BPB、BPS处理HL-7702细胞24 h后,通过油红O染色观察细胞内脂肪蓄积情况;GPO-PAP酶法测定细胞内甘油三酯含量;实时PCR测定细胞内甘油三酯合成相关基因LIPIN2和DGAT2 mRNA的表达水平。结果油红O染色显示,BPA、BPAF、BPB、BPS组细胞内均可观察到大小不等的红色脂滴。甘油三酯含量测定发现,1、50μmol/L BPA组,10、50μmol/L BPAF组,1、10、50μmol/L BPB组,50μmol/L BPS组细胞内甘油三酯含量明显增加;实时PCR结果显示,10μmol/L BPAF组,10μmol/L BPB组及1、10μmol/L BPS组细胞内LIPIN2 mRNA表达水平明显升高,50μmol/L BPA组、10μmol/L BPAF组及10、50μmol/L BPB组和1μmol/L BPS组细胞内DGAT2 mRNA表达水平明显升高。结论BPA、BPAF、BPB、BPS可通过上调DGAT2 mRNA表达促进细胞内甘油三酯合成增加,BPAF、BPB、BPS还可通过上调LIPIN2 mRNA表达促进细胞内甘油二酯合成,导致HL-7702细胞内脂肪蓄积。

Objective To investigate whether BPA and its substitutes BPAF,BPB,and BPS can induce lipid accumulation in hepatocytes.Methods HL-7702 cells were treated with BPA,BPAF,BPB,or BPS for 24 h.Lipid droplet accumulation in cells was observed via oil red O staining,and triglyceride content was determined through the GPO-PAP chemical-enzymatic method.In addition,qRT-PCR was used to detect the expression of triglyceride synthesis-related genes.Results Red lipid droplets of different sizes could be observed in the BPA,BPAF,BPB,and BPS groups.The intracellular triglyceride content increased significantly under 1 and 50μmol/L BPA,10 and 50μmol/L BPAF,1,10,and 50μmol/L BPB,and 50μmol/L BPS.LIPIN2 mRNA expression level increased significantly under 10μmol/L BPAF,10μmol/L BPB,and 1 and 10μmol/L BPS.DGAT2 mRNA expression increased significantly under 50μmol/L BPA,10μmol/L BPAF,10 and 50μmol/L BPB,and 1μmol/L BPS.Conclusion BPAF,BPB,and BPS can increase intracellular triglyceride synthesis by upregulating LIPIN2 and DGAT2 mRNA expression,leading to intracellular fat accumulation and increased triglyceride content in HL-7702 cells.