关键词: 肝纤维化, 肝星状细胞, 辛二酰苯胺异羟肟酸, 组蛋白修饰, 细胞凋亡

Abstract: Objective To determine the effects of histone deacetylase inhibitor SAHA on the cell proliferation and apoptosis of the human hepatic stellate cell line LX-2.The possible underlying mechanisms were also investigated. Methods The LX-2 cells were treated with SAHA in vitor.The morphology of LX-2 cells in diff- erent concentrations groups were observed by inverted microscope;the proliferation of LX-2 cells was measured by MTT assay;the Annexin V-FITC and PI staining was used to detect the apoptosis rates of LX-2 cells by flow cytometry and fluorescence microscope;the expression of α-SMA,collagen I,acH3K9,acH3K14 and acH3K18 were detected by Western blotting.Results The morphology change of LX-2 cells showed that SAHA could inhibit the proliferation rate of LX-2 cells and in a dose dependent manner(P<0.05). The LX-2 cells were sensitive to SAHA along with time increasing ,and in a time- dependent manner(P<0.05).Western blotting showed that the expression levels of α-SMA and collagen-I were significantly lower(P<0.05) ,on the contrary ,the acetylation levels of acH3K9,acH3K14 and acH3K18 were significantly higher (P<0.05).Conclusions The increased acetylation levels of the histone acH3K9,acH3K14 ,acH3K18 and the lower expressed α-SMA and collagen-I in LX-2 cells may be one of the mechanismsof SAHA.

Key words: Hepatic stellate cells, suberoylanilide hydroxamic acid, Histone modifications, Liver fibrosis, apoptosis