三氧化二砷抑制兔血管平滑肌细胞增殖及诱导凋亡的相关机制

Mechanism of arsenic trioxide inhibiting rabbits vascular smooth muscle cells and inducing apoptosis

目的 研究三氧化二砷（As2O3）对免血管平滑肌细胞（VSMC）的抑制增殖、促进凋亡及诱导细胞周期停滞的作用.方法 经组织块贴壁法原代培养的兔VSMC,应用3H-胸腺嘧啶胞苷渗入法、透射电镜、TUNEL法、流式细胞术和基因芯片测定As2O3对VSMC的细胞活力、生长、增殖及凋亡.结果 随着三氧化二砷浓度的增加显著抑制了细胞生长,且呈剂量依赖性,透射电镜下可见凋亡小体,TUNEL检测出现了凋亡细胞,流式细胞术出现了典型的凋亡峰.基因芯片扫描杂交结果数据显示其中26条基因表达有差异.结论 As2O3对VSMC具有抑制增殖、促凋亡、阻滞细胞周期进程的作用.

Objective To study the anti-proliferation , pro-apoptosis and cell cycle blocking effects of arsenic trioxide （As2O3） on rat vascular smooth muscle cells （VSMC） . Methods The effects of As2O3 on VSMCs viability , growth, proliferation and change of cell cycle of VSMCs were assayed by thiazoyl blue tetrazolium bromide assay （MTT） , 3 H-thymidine incorporation method, transmission electron microscopy, TUNEL ,flow cytometry, and gene chip. Results As2O3 inhibited the growth of VSMCs dose-dependently. Typical apoptoic cellular changes were found after As2O3 treatment. Transmission electron microscopy showed apoptotic body and TUNEL showed apoptotic cell in the treated cells. A peak of degrade DNA could be observed by flow cytometry. There were 26 differentially expressed genes identified. Conclusion These results suggest that As2O3 can inhibit the proliferation and block the cell cycle progression in VSMCs.