大黄素自身抑制血管平滑肌细胞迁移和增殖Emodin inhibit the migration and proliferation of vascular smooth muscle cell independent on metabolism
王翔飞,葛均波,孙爱军,徐丹令,王克强
摘要(Abstract):
目的探讨大黄素对血管平滑肌细胞迁移和增殖的作用以及大黄素在血管平滑肌细胞中是否存在代谢过程。方法采用Transwell迁移系统和MTT法观察大黄素对血管平滑肌细胞迁移和增殖的影响。结果大黄素能显著抑制平滑肌细胞迁移,5μg/mL大黄素抑制率为83·3%;大黄素呈浓度和时间依赖性抑制平滑肌细胞增殖。然而,血管平滑肌细胞作用24h后,上清液中的大黄素浓度并无显著降低;细胞色素p450氧化酶诱导剂或者抑制剂没有改变大黄素的细胞毒性作用或者细胞内活性氧水平。大黄素的主要代谢酶(细胞色素p450氧化酶)基因表达水平没有显著的上调。结论大黄素能够抑制血管平滑肌细胞的迁移和增殖,并且不被平滑肌细胞代谢,可能作为药物涂层支架的药物。
关键词(KeyWords): 大黄素;肌,平滑,血管;细胞
基金项目(Foundation): 国家“863”计划(2002AA326110);; 国家自然科学基金资助项目(30270545)
作者(Author): 王翔飞,葛均波,孙爱军,徐丹令,王克强
参考文献(References):
- [1]Chervu A,Moore WS.An overview of intimal hyperplasia.Surg Gynecol Obstet,1990,171:433-447.
- [2]Heckenkamp J,Gawenda M,Brunkwall J.Vascular restenosis.Basic science and clinical implications.J Cardiovasc Surg(Torino),2002,43:349-357.
- [3]Suzuki T,Kopia G,Hayashi S,et al.Stent-based delivery of sirolimus reduces neointimal formation in a porcine coronary model.Circulation,2001,104:1188-1193.
- [4]Heldman AW,Cheng L,Jenkins GM,et al.Paclitaxel stent coating inhibits neointimal hyperplasia at4weeks in a porcine model of coronary restenosis.Circulation,2001,103:2289-2295.
- [5]Zhu F,Liu XG,Liang NC.Effect of Emodin and Apigenin on Invasion of Human Ovarian Carcinoma HO-8910PMCells In Vitro.Ai Zheng,2003,22:358-362.
- [6]Kuo YC,Sun CM,Ou JC,et al.Atumor cell growthinhibitor fromPolygonumhypoleucumOhwi.Life Sci,1997,61:2335-2344.
- [7]Tanaka H,Morooka N,Haraikawa K,et al.Metabolic activation of emodinin the reconstituted cytochrome P-450systemof the hepatic microsomes of rats.Mutat Res,1987,176:165-170.
- [8]Wang HW,Chen TL,Yang PC,et al.Induction of cytochromes P4501A1and1B1byemodinin humanlungadenocarcinoma cell line CL5.Drug Metab Dispos,2001,29:1229-1235.
- [9]Morita H,Umeda M,Masuda T,et al.Cytotoxic and mutagenic effects of emodin on cultured mouse carcinoma FM3Acells.Mutat Res,1988,204:329-332.
- [10]Nebert DW,Roe AL,Dieter MZ,et al.Role of the aromatic hydrocarbon receptor and[Ah]gene battery in the oxidative stress response,cell cycle control,and apoptosis.Biochem Pharmacol,2000,59:65-85.
- [11]Mueller SO,Eckert I,Lutz WK,et al.Genotoxicity of the laxative drug components emodin,aloe-emodin and danthron in mammalian cells:topoisomerase II mediated?Mutat Res,1996,371:165-173.
- [12]Jayasuriya H,Koonchanok NM,Geahlen RL,et al.Emodin,a proteintyrosine kinase inhibitor from Polygonumcuspidatum.J Nat Prod,1992,55:696-698.
- [13]Yim H,Lee YH,Lee CH,et al.Emodin,an anthraquinone derivative isolatedfromthe rhizomes of Rheumpalmatum,selectively inhibits the activity of casein kinase II as a competitive inhibitor.Planta Med,1999,65:9-13.
- [14]Huang HC,Chang JH,Tung SF,et al.Immunosuppressive effect of emodin,a free radical generator.Eur J Pharmacol,1992,211:359-364.