硫化砷对骨髓增生异常综合征骨髓单个核细胞体外凋亡的作用

Apoptosis of In Vitro Cultured BMMNC from MDS Patients Induced by Arsenic Sulfide

为了研究硫化砷(As2S2)在体外对骨髓增生异常综合征患者骨髓单个核细胞增殖的影响,并探讨其可能的作用机制,采用MTT法、流式细胞术、RT-PCR等多参数检测不同浓度As2S2诱导MDS细胞的凋亡。结果表明:①低浓度(0-0.6mg/L)的硫化砷对MDS细胞无明显抑制作用;②相对高浓度的硫化砷(1.5-50mg/L)对低危组MDS以及高危组MDS的单个核细胞均有诱导凋亡作用,且呈时间浓度依赖关系;bcl-2mRNA在As2S2作用后表达明显下调,bcl-2/bax比例明显下降(P<0.05);③MDS病人存在骨髓造血细胞的过度凋亡。结论:MDS病人存在骨髓造血细胞的过度凋亡;低浓度的硫化砷对MDS细胞没有明显的增殖抑制作用,高浓度的硫化砷主要通过诱导凋亡使MDS细胞死亡。

The aim of this study was to investigate the inhibition effect of arsenic sulfide （ As2S2 ） on the growth of in vitro cultured BMMNC from MDS patients and to explore its possible cellular and molecular mechanisms. The apoptosis of MDS cells induced by As2S2 solution of different concentrations were studied with MTF, flow cytometry, and RT- PCR. The results showed that （ 1 ） low concentration of As2S2 （0 - 0.6 mg/L） had no marked inhibition effect on proliferation of MDS cells; （2） after treatment with 1.5 -50 mg/L of As2S2, both low risk MDS cells and high risk MDS cells presented typical features of apoptosis with a dose-dependent manner, the expression of bcl-2 mRNA and the ratio of bcl-2/bax obviously decreased after As2S2 treatment （ P 〈 0.05 ） ; （3） BMMNC from MDS patients had higher apoptosis ratio than that of BMMNC from control. It is concluded that BMMNC excessive apoptosis exists in MDS patients; low concentration of As2S2 （0 -0.6mg/L） shows no inhibition effect on proliferation of MDS cells;high concentration of As2S2 （ 1.5 - 50mg/L） induces apoptosis of MDS cells.