萘哌地尔衍生物YMⅢ抗AngⅡ诱导SHR血管平滑肌细胞增殖的作用  

Antiproliferative effect of naftopidil ramification YMⅢ on vascular smooth muscle cells of spontaneously hypertensive rat

作　　者：邱敏[1,2] 杨征[1,3] 李利生[1] 吴芹[1] 金凤[1] 黄燮南[1] 

机构地区：[1]遵义医学院药理学教研室,贵州遵义563000 [2]包头医学院药学院,内蒙古包头014060 [3]包头医学院第一附属医院心内二科,内蒙古包头014010

出　　处：《中国药理学通报》2012年第9期1248-1252,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30060087)

摘　　要：目的观察萘哌地尔衍生物YMⅢ对血管紧张Ⅱ(AngⅡ)诱导的自发性高血压大鼠(SHR)血管平滑肌细胞(VSMC)增殖的影响,并初探其作用机制。方法以组织块贴壁法培养SHR VSMC,应用MTT比色法、3[H]-TdR参入法、流式细胞技术、电镜技术和real time RT-PCR分别观察VSMC在AngⅡ刺激下的细胞增殖、DNA合成、细胞周期、细胞超微结构和Agt、c-myc基因表达的变化,及观察YMⅢ对上述指标的影响。结果 AngⅡ1μmol.L-1明显促进VSMC增殖和DNA合成;而YMⅢ0.01、0.05、0.10μmol.L-1可呈浓度依赖性地抑制AngⅡ所致VSMC增殖活性、DNA合成、细胞周期增殖指数的升高,改善细胞超微结构,并使AngⅡ升高的Agt、c-myc mRNA表达下调。结论 YMⅢ可明显抑制AngⅡ诱导的SHR VSMC增殖,作用机制可能与其抑制Agt、c-myc mRNA表达,从而抑制细胞DNA合成和细胞周期的进展有关。Aim To investigate the effect of YM Ⅲ, a ramification of naftopidil, on Angiotensin Ⅱ （ Ang Ⅱ ） - induced proliferation of vascular smooth muscle cell （VSMC） from spontaneously hypertensive rat （SHR） in vitro and probe preliminarily its mechanisms of action. Methods In cultured VSMCs from SHR, the changes of cell proliferation, DNA synthesis, cell cycle progress, cell ultramicrostructure and Agt, c-myc mRNA expressions induced by AngⅡ were evaluated by MTY assay, [ 3 ^H ] -TdR incorporating method, flow cytometry assay, transmission electron microscopy technigue and real time RT-PCR, respectively, and the influences of YM Ⅲ on the above parameters were observed. Results Compared with the model controlgroup, YMⅢ 0. 01,0. 05,0. 10 μmol ·L-1 could concentration-dependently inhibit the cell prolifetation and the elevated rate of [ 3^H ]-TdR incorporation induced by Ang Ⅱ 1 ixmol ~ L-1 ; this agent could also block the cell cycle progress, improve the cell ultramicrostructure, and down-regulate the elevated Agt and c- myc mRNA expressions induced by Ang Ⅱ. Conclusion YM m has an inhibitory effect on the proliferation of SHR VSMC in vitro, which may be related to the down-regulation of Agt and c-myc mRNA expressions, leading to inhibitions of DNA synthesis and cell cycle progress.

关 键 词：萘哌地尔 血管紧张素Ⅱ 血管平滑肌细胞 增殖 血 管紧张素原 c-myc 

分 类 号：R322.74[医药卫生—人体解剖和组织胚胎学] R329.24[医药卫生—基础医学]