双环铂对人主动脉平滑肌细胞和内皮细胞增殖影响的初步体外实验研究  

Preliminary Effect of Dicycloplatin on Proliferation of Human Aortic Smooth Muscle Cells and Human Aortic Endothelial Cells In Vitro

作　　者：许连军[1] 高润霖[2] 吴超[2] 叶珏[1] 宋莉[1] 钱鑫[3] 

机构地区：[1]北京协和医学院 中国医学科学院 阜外心血管病医院中心实验室,北京市100037 [2]北京协和医学院 中国医学科学院 阜外心血管病医院冠心病诊治中心,北京市100037 [3]北京协和医学院 中国医学科学院 阜外心血管病医院内分泌实验室,北京市100037

出　　处：《中国循环杂志》2012年第6期454-457,共4页Chinese Circulation Journal

摘　　要：目的:通过体外实验,研究双环铂对人主动脉平滑肌细胞(HASMC)和人主动脉内皮细胞(HAEC)增殖的影响,探讨其成为支架携带药物的可能性。方法:3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基胺)-2-(4-苯磺基)-2氢-四唑盐(MTS)法评价双环铂对HASMC和HAEC增殖的影响。探索不同浓度和不同作用时间条件下双环铂对HASMC和HAEC增殖抑制率的影响;双环铂对HASMC和HAEC半数抑制浓度的差异;以西罗莫斯作为阳性对照组,探索双环铂对HASMC和HAEC抗增殖作用的最低有效浓度。结果:双环铂对HASMC和HAEC的增殖抑制作用呈时间和浓度依赖性。双环铂对HASMC和HAEC的半数增殖抑制浓度分别为3.47μg/ml和72.44μg/ml。双环铂浓度为10 ng/ml～10μg/ml时,对HASMC有显著抑制作用(P<0.05)。双环铂浓度为10μg/ml时,对HAEC有显著抑制作用(P<0.01)。阳性对照药物西罗莫斯在纳克(ng)水平对HASMC和HAEC的增殖也有明显的抑制作用。结论:双环铂对HASMC和HAEC的增殖抑制作用呈时间和浓度依赖性。双环铂对HAEC的最低抑制浓度比对HASMC的最低抑制浓度高1000倍。尽管双环铂对细胞增殖的作用弱于西罗莫斯,但是其明显抑制血管平滑肌细胞增生而较少抑制血管内皮细胞增生的特性,使其有可能成为药物洗脱支架所携带的药物。Objective： To investigate the effect of dicycloplatin on proliferation of human aortic smooth muscle cells （HASMC） and hu- man aortic endothelial cells （HAEC） in vitro and to approach its potential possibility for being used as a carrier in drug-eluting stents. Methods ： HASMC and HAEC were incubated with dicycloplatin at 5 different doses as 1 ng/ml, 10 ng/ml, 100 ng/ml, 1 ug/ ml, and 10 ug/ml respectively. Sirolimus was used as positive control at 3 different doses as 1 ng/ml, 10 ng/ml and 100 ng/ml respectively. The optical density value of HASMC and HAEC was measured by MTS [ 3-（4,5-dimethylthiazol-2-yl）-5-（3-carboxy- methoxyphenyl）-2-（4-sulfophenyl）-2H-tetrazolium ] assay. The cell proliferation and 50% inhibition rate were calculated respec- tively. Results： The inhibition of dicycloplatin on HASMC and HAEC proliferation showed a time- and dose-dependent manner. Dicycloplatin dose for reaching 50% inhibition on HASMC proliferation was 3.47 ug/ml, on HAEC was 72.44 ug/ml respectively. Dicycloplatin dose at 10 ng/ml- 10 ug/ml could remarkably inhibit HASMC proliferation,P〈0. 05, and dicycloplatin 10ug/ml could significantly inhibit HAEC proliferation, P〈 0. 01. The positive control, sirolimus may also obviously inhibit HASMC and HAEC proliferation at the dose of nano-gram level. Conclusion： Dicycloplatin could obviously inhibit HASMC proliferation and less inhibit HAEC proliferation, this characteristic may have potential possibility for it being used as a carrier in drug-eluting stents.

关 键 词：血管平滑肌细胞 内皮细胞 双环铂 西罗莫斯 再狭窄 药物洗脱支架 

分 类 号：R541.4[医药卫生—心血管疾病]