三氧化二砷纳米微粒对抑制兔血管平滑肌细胞增殖作用的实验研究  

Experimental study on effect of arsenic trioxide on vascular smooth muscle cells

作　　者：卢勤[1] 安艳丽[1] 王子好[2] 张东生[2] 牛焕章[1] 方娟娟[3] 滕皋军[1] 

机构地区：[1]东南大学附属中大医院放射科,南京210009 [2]东南大学基础医学院病理学系 [3]东南大学基础医学院病理生理学系

出　　处：《中华放射学杂志》2007年第4期423-426,共4页Chinese Journal of Radiology

基　　金：国家自然科学基金(30300094);江苏省自然科学基金(BK200507)

摘　　要：目的了解纳米微粒与普通剂型的三氧化二砷(As_2O_3)对抑制体外培养的兔血管平滑肌细胞(VSMC)增殖作用的差别。方法对照组为不加药物的细胞,实验组为3 μmol/L 纳米微粒和普通剂型的 As_2O_3,干预体外培养的兔 VSMC 细胞72 h,进行四唑氮盐(MTT)染色测定细胞吸光度(A)值。用流式细胞仪检测细胞凋亡情况,提取细胞 DNA,进行凝胶电泳分析,将3组的结果进行比较。结果 3 μmol/L 纳米剂型的 As_2O_3干预细胞,细胞数量随作用时间的延长逐渐减少,细胞生长明显受抑制,而普通剂型干预细胞,生长受抑制程度较纳米剂型弱。24 h 时,对照组、3 μmol/L 普通剂型组与纳米组,A 值分别为0.68±0.10、0.58±0.12、0.33±0.12,48 h 时分别为0.79±0.11、0.48±0.14、0.28±0.11,72 h 时分别为0.96±0.13、0.34±0.15、0.20±0.06,差异均有统计学意义(H 值分别为10.934、15.039、15.539,P 值均<0.01)。流式细胞仪检测,纳米剂型 As_2O_3、普通剂型 As_2O_3干预及对照组的细胞干预48 h,细胞增殖率分别为44.97%、58.54%、74.02%,早期凋亡率分别为16.89%、11.27%、11.20%,晚期凋亡率分别为26.56%、23.60%、12.46%,坏死细胞分别为11.58%、6.59%、2.32%。DNA 电泳,As_2O_3干预细胞,可见凋亡梯形条带,部分细胞坏死,呈模糊的无间隔片状条带。纳米剂型药物作用的细胞 DNA 条带,梯形条带更多、更模糊。结论 As_2O_3可以抑制体外培养的 VSMC 增殖,且纳米剂型 As_2O_3较普通剂型的 As_2O_3对细胞抑制作用更强。Objective To investigate the effect of arsenic trioxide （As2O3 ） nanoparticles on rabbit vascular smooth muscle cells in vitro in comparison with normal form As2O3. Methods The rabbit vascular smooth muscle cells were cultured in vitro. Nano and normal forms of As2O3 with drug concentrations of 3μmol/L were added into the cells. Cell proliferation curve was drawn according to the light absorption values of MTT test. Flow cytometry was applied to observe the apoptosis. DNA was extracted and underwent electrophoresis. Results Cell proliferation treated with the 3 μmlo/L concentration of As2 O3 was inhibited. Cell growth was inhibited markedly with increased treatment time, and the inhibition effect of nano drug form seemed stronger than that of normal form. MTT light absorption values of cells treated at 24,48 and 72 h showed statistically significant difference （ H = 10. 934, 15. 039,15. 539, P 〈 0. 01 ）. With flow cytometry test, the cell proliferation rotes of 3 μmol/L nano drug form of As2O3, normal drug form of As2O3 and control group of cells without As2O3 were 44. 97%, 58.54%, 74. 02% respectively. The early apoptosis rates were 16.89%, 11.27%, 11.20%, late apoptosis rates were 26.56%, 23.60%, 12.46%, and necrosis rates were 11.58%, 6. 59%, 2. 32% respectively. Agarese gel electrophoresis showed ＂ladder＂ strand of DNA, with more strands and obscurity for nano drug form treated cells. Conclusion Arsenic trioxide may inhibit the growth of rabbit vascular smooth muscle cells. The nano drug form showed stronger inhibition effect than that of the normal drug form.

关 键 词：砷剂 血管平滑肌 细胞增殖 三氧化二砷纳米微粒 介入性放射学 

分 类 号：R96[医药卫生—药理学]