Abstract: Objective To explore the effect of occupational mercury exposure on fibrosis in human hepatic stellate cell line（LX-2） based on the microRNA-143-3p（miR-143-3p）-angiopoietin-like protein 8（ANGPTL8） pathway. Methods Human hepatic stellate cells LX-2 were digested with trypsin and plated in a 96-well plate at 4×10³ cells/well. After incubation for 24 hours,different concentrations of HgCl₂（0,100,200,400 μmol/L） were added. The cells were incubated for 72 hours,the cell proliferation level,the number of monoclonal formation,the apoptosis level,and the G2/M phase of the cell cycle were measured. The cell fibrosis indicators α-smooth muscle actin（α-SMA） and type collagen A1（Col1a1） were determined by immunofluorescence assay,the levels of inflammatory indicators tumor necrosis factor alpha（TNF-α）,interleukin-6（IL-6）,and interleukin-18（IL-18） were measured by enzyme-linked immunosorbent assay,and the levels of cellular miR-143-3p and ANGPTL8 were measured by RT-PCR and Westen-blot methods. Results Compared with the control group（0.00 μmol/L HgCl₂）,the survival rate,number of monoclonal formations,and levels of fibrosis indicators α-SMA and Col1a1 in the exposure dose groups of 2.50,5.00,and 10.00 μmol/L HgCl₂ were significantly increased（all P<0.01）,while apoptosis rate and cell cycle G2/M phase levels were significantly reduced（all P<0.01）. With the increase of HgCl₂ exposure dose,the survival rate,the number of monoclonal formation,and the levels of fibrosis indicators α-SMA and Col1a1 in each dose group of HgCl₂ gradually increased（all P<0.01）,and the apoptosis rate and cell cycle G2/M phase levels gradually decreased（all P<0.01）. Compared with the control group（0.00 μmol/L HgCl₂）,the expression levels of miR-143-3p in the exposure dose groups of 2.50,5.00 and 10.00 μmol/L HgCl₂（4.83±0.87 vs 2.92±0.62,1.91±0.34,0.85±0.10）were significantly reduced（all P<0.01）,while the expression levels of ANGPTL8 mRNA protein（0.95±0.11 vs 1.59±0.16,2.84±0.29,3.69±0.38;0.23±0.06 vs 0.46±0.12,0.83±0.17,1.49±0.21）,TNF-α,IL-6,and IL-18 increased significantly（all P<0.01）. With the increase in HgCl2 exposure dose,the expression levels of miR-143-3p in each dose group of HgCl₂ gradually decreased（2.92±0.62 vs 1.91±0.34 vs 0.85±0.10）,while the expression levels of ANGPTL8 mRNA protein（1.59±0.16 vs 2.84±0.29 vs 3.69±0.38,0.46±0.12 vs 0.83±0.17 vs 1.49±0.21）,TNF-α,IL-6 and IL-18 gradually increased（all P<0.01）. Conclusion Mercury exposure can promote abnormal proliferation of human hepatic stellate cell line（LX-2）,induce fibrosis progression,inhibit cell apoptosis,and induce cell cycle arrest. The mechanism is related to the inhibition of miR-143-3p expression in human hepatic stellate cell line（LX-2） by mercury exposure,which in turn promotes high expression of ANGPTL8.

Key words: MicroRNA-143-3p, Angiopoietin-like protein 8, Mercury, Human hepatic stellate cell line, Fibrosis