目的 通过观察不同浓度三氧化二砷(As2O3)对内皮细胞增殖及分泌一氧化氮(NO)的影响, 初步从内皮细胞角度评价As2O3防治PTCA术后再狭窄的作用。方法 以不同浓度As2O3溶液(0.01、0.1、0.5、1、5、10 μmol/L)作用于传代培养的EVC-304细胞, 分别培养24、48、72 h测定内皮细胞对 3H-TdR摄取量, 以硝酸还原酶法测定内皮细胞培养液NO含量。结果 As2O3浓度低于1 μmol/L时对内皮细胞摄取3H-TdR无抑制作用。As2O3浓度低于0.1 μmol/L时对内皮细胞分泌NO无明显抑制作用;As2O3浓度0.5~10 μmol/L时抑制内皮细胞分泌NO。结论 As2O3 浓度低于0.1 μmol/L对内皮细胞增殖及分泌NO均无明显抑制作用;0.1~1 μmol/L范围内只对内皮细胞分泌NO的功能有轻度影响, 但不抑制内皮细胞的增殖;而较高浓度的As2O3对内皮细胞增殖及分泌NO均有明显抑制, 而且抑制作用随浓度增高而增强。As2O3 用于防治PTCA术后再狭窄应采取低较浓度。
Abstract
Objective To investigate the effect of As2O3 on proliferation of human umbilical endothelial cells, and nitric oxide(NO)release, and to evaluate the value of NO in inhibiting restenosis. Methods Cultured cells were divided into seven groups, one as control group, the other six groups were incubated with As2O3 at deferent concentrations(0.01, 0.1, 0.5, 1, 5, 10 μmol/L).Effect of As2O3 on proliferation of human umbilical endothelial cells(ECV-304) was detected by 3H-TdR assay at 24 h, 48 h, 72 h and nitric oxide (NO) production was elected. Results When the concentration of As2O3 was lower than 1 μmol/L, it had no effect on endothelial cells proliferation.When the concentration of As2O3 was lower than 0.1 μmol/L, it had no effect on NO production.NO production was reduced in dose dependent manner, when endothelial cells were incubated in As2O3 within the concentration range of 0.5~10 μmol/L. Conclusions When the concentration of As2O3 is lower than 0.1 μmol/L, it has no effect on endothelial cells proliferation and NO production. As2O3 within the concentration range of 0.1~1 μmol/L can reduce NO production, but has no effect on endothelial cells proliferation. As2O3 at low concentration may be used to reduce restenosis.
关键词
三氧化二砷 /
内皮细胞 /
增殖 /
一氧化氮
Key words
arsenic trioxide /
endothelial cells /
proliferation /
nitric oxide
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Hiltunen M O, Laitimen M, Turunen M P, et al. Intravascular adenovirus-mediated VEGF-C gene transfer reduces neointimal formation in balloon denuded rabbit aorta[J].Circulation, 2000, 102(18):2262-2268.
[2] Liu Y, Wang X, Lu J. Dynamic observation of artery endothelial cell layers in response to bare metal stent and paclitaxel-eluting stent in vitro[J]. Interv Cardiol, 2014, 27(2):182-190.
[3] Kitamura N, Hasebe T, Matsumoto T, et al, Basic fibroblast growth factor as a potential stent coating material inducing endothelial cell proliferation[J]. Atheroscler Thromb, 2014, 21(5):477-485.
[4] Yamamoto T, Shibata R, Ishii M, et al.Therapeutic reendothelialization by induced pluripotent stem cells after vascular injury--brief report [J].Arterioscler Thromb Vasc Biol, 2013, 33(9):2218-2221.
[5] 邵建伟, 吴宗贵, 李 莉, 等. 三氧化二砷诱导平滑肌细胞凋亡的实验研究[J].第二军医大学学报, 2000, 21(4):330-333.
[6] 田 刚, 张春晓, 孙 中, 等.冠状动脉支架置入术后支架内再狭窄的相关因素分析[J].山东医药, 2012, 52(34):53-55.
[7] 邵建伟, 华尔铨, 吴宗贵, 等.三氧化二砷诱导大鼠血管平滑肌细胞凋亡的实验研究[J].中国药学杂志, 2002, 37(12):910-913.
[8] 栾天竹, 梅 宇, 许冬秀, 等. 三氧化二砷对球囊拉伤后兔血管平滑肌细胞作用的实验研究[J].中华医学杂志, 2003, 83(3):859-861.
[9] Zhao Z, Huang C, Wang J, et al. Effect of arsenic trioxide on inhibition restenosis after rabbit vascularinjury and its mechanism [J].Chin Med J (Engl), 2002, 115(11):1608-1614.
[10] Gong F, Cheng X, Wang S, et al. Heparin-immobilized polymers as non-inflammatory and non-thrombogenic coating materials for arsenic trioxide eluting stents [J].Acta Biomater, 2010, 6(2):534-546.
[11] Fang C H, Song Y S, So B I, et al. Concentration-dependent differential effects of udenafil on viability, proliferation, and apoptosis in vascular endothelial and smooth muscle cells [J].Indian J Pharmacol, 2014, 46(3):292-297.
[12] Axel D I, Kunert W, Grogelman C, et al. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery [J].Circulation, 1997, 96(2):636-645.
