目的:探讨高糖诱导下应用5-氮杂-2'-脱氧胞苷(5-Aza-dC)和曲古霉素A(TSA)对胰岛 β 细胞NIT-1细胞株增殖及PDX-1启动子区甲基化及其表达的影响.方法:胰岛β细胞株予33.3 mmol/L葡萄糖浓度处理后随机分为:空白对照(NC)组、高糖诱导(HG)组、5-Aza-dC干预组、TSA干预组、5-Aza-dC+TSA联合干预组,检测细胞增殖情况、胰岛素释放水平、PDX-1启动子区甲基化状态及其表达水平的变化.结果:5-Aza-dC和TSA单独或联合干预可增加NIT-1细胞增殖率和胰岛素分泌量,降低PDX-1启动子区甲基化产物,增加PDX-1 mRNA相对表达量,并且联合组比单药组效果更加明显(均P<0.05).结论:5-Aza-dC和TSA可以激活高糖诱导下失表达的PDX-1,进而恢复胰岛β细胞功能,两药联合具有协同效应.%Objective To investigate the effects of 5-aza-2'-deoxycytidine (5-Aza-dC) alone or combined with trichostatin A(TSA) on cell proliferation, promoter methylation and mRNA expression level of PDX-1 gene in pancreatic β cells induced by high glucose toxicity. Method NIT-1 cells were treated in vitro by high glucose (33.3 mmol/L), then divided into five groups, control group, HG grpup, 5-Aza-dC treatment group, TSA interfere group and 5-Aza-dC + TSA group. Proliferation of NIT-1 cells, insulin secretion, promoter methylation and mRNA expression of PDX-1 gene were detected respectively. Results 5-Aza-dC and TSA alone or in combination could promote cell proliferation and recover insulin secretion in NIT-1 cells , could also reduce PDX-1 gene methylation and enhance expression of PDX-1 mRNA. Compared with single-treatment group , combined group was significantly different (all P < 0.05). Conclusion 5-Aza-dC and TSA could activate the expression of PDX-1 and, then recover insulin secretion in NIT-1 cells induced by high glucose. Combination of them had synergistic effect.
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