三丁酸甘油酯诱导白血病细胞分化及凋亡机制的研究

为了探讨组蛋白去乙酰化酶抑制剂三丁酸甘油酯（tributyrin,TB）诱导NB4、K562白血病细胞分化和（或）凋亡的作用机制,利用Western blot方法及逆转录聚合酶链反应（RT-PCR）检测TB作用前后NB4、K562细胞组蛋白H3乙酰化水平以及p21^WAF1表达量的改变.结果表明：NB4（或K562）细胞经TB0.1 mmol/L（或TB 0.5 mmol/L）作用16小时后可见组蛋白H3乙酰化水平明显上升,并有剂量依赖效应.NB4、K562细胞经TB 0.1 mmol/L作用后可见p21^WAF1 mRNA表达上调,且具有剂量依赖效应.p21^WAF1 mRNA的这种上调开始于TB作用2小时后,16小时达高峰,可维持48小时.结论：TB诱导NB4、K562细胞发生分化和（或）凋亡的机制与TB引起细胞组蛋白高乙酰化和继而上调p21^WAF1表达有关.

Mechanism of Differentiation and Apoptosis in Leukemia Cells Induced by Tributyrin

To elucidate the possible mechanism of differentiation and /or apoptosis in NB4, K562 cells induced by tributyrin (TB), a histone deacetylase inhibitor (HDACi), the level of acetylated histone H3 was detected by Western blot, p21~ WAF1expression was detected by semi-quantitative RT-PCR. The results showed that histone H3 hyperacetylation was detected in NB4 (or K562) cells after treatment with TB 0.1 mmol/L(or TB 0.5 mmol/L) for 16 hours in a dose-dependent manner. p21~ WAF1 dose-dependently increased at RNA level in these two cell lines treated by TB 0.1 mmol/L. The level of p21~ WAF1mRNA increased at 2 hours after TB treatment, reaching peak at 16 hours, and maintaining for 48 hours. In conclusion, the mechanism of differentiation and apoptosis in NB4, K562 cells induced by tributyrin may associate with its up-regulation of acetylated histone and p21~ WAF1mRNA level.