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为了探讨丙戊酸钠(sodium valproate,VPA)对骨髓增生异常综合征细胞株MUTZ-1的生长抑制及诱导凋亡作用,采用四甲基偶氮唑蓝(MTT)比色法检测VPA对细胞生长的抑制作用;采用光学显微镜和电子显微镜观察VPA作用后细胞形态的变化;应用流式细胞术(FCM)检测不同浓度VPA作用后细胞凋亡的比例和细胞周期分布的变化。结果显示:VPA对MUTZ-1细胞的生长抑制作用呈现时间和剂量依赖性;经4mmol/LVPA处理MUTZ-1细胞72小时后,细胞呈现典型的凋亡形态特征,光学显微镜下可见凋亡细胞胞体固缩、核固缩、核碎裂及凋亡小体;透射电子显微镜下可见凋亡细胞核染色质边集、胞浆浓缩、密度增加,胞浆内大小不规则的染色质团块;流式细胞术结果表明,细胞凋亡率随着VPA浓度的增加而逐步增高,G0/G1期细胞比例随着VPA浓度的增加而逐渐增多,S期细胞比例逐渐减低,细胞被阻滞在G0/G1期。结论:VPA通过G0/G1期阻滞诱导MUTZ-1细胞凋亡,从而抑制MUTZ-1细胞增殖。
In order to investigate the effect of sodium valproate (VPA) on the growth and apoptosis of myelodysplastic syndrome cell line MUTZ-1, MTT assay was used to detect the effect of VPA on cells The changes of cell morphology after VPA treatment were observed by light microscope and electron microscope. The percentage of apoptotic cells and cell cycle distribution were detected by flow cytometry (FCM). The results showed that: VPA inhibited the growth of MUTZ-1 cells in a dose-and time-dependent manner; MUTZ-1 cells treated with 4mmol / LVPA for 72 hours exhibited typical morphological features of apoptosis. Under light microscope, apoptotic cells Pyknosis, nuclear pyknosis, nuclear fragmentation and apoptotic bodies. Apoptotic nuclear chromatin margins, cytoplasmic condensation, increased density and cytoplasmic irregular chromatin masses were observed under transmission electron microscope. The result of cytology showed that the rate of apoptosis increased gradually with the increase of VPA concentration. The proportion of cells in G0 / G1 phase increased gradually with the increase of VPA concentration, and the proportion of cells in S phase decreased gradually. The cells were arrested at G0 / G1 period. Conclusion: VPA can induce the apoptosis of MUTZ-1 cells through G0 / G1 phase arrest and thus inhibit the proliferation of MUTZ-1 cells.