萘哌地尔抗大鼠血管平滑肌细胞增殖的作用  

The antiproliferation effect of naftopidil in vascular smooth muscle cells of rats

作　　者：李利生[1] 孙安盛[1] 余丽梅[1] 吴芹[1] 黄燮南[1] 袁牧[2] 

机构地区：[1]遵义医学院药理学教研室,贵州遵义563003 [2]贵州省中国科学院天然产物化学重点实验室,贵州贵阳550002

出　　处：《中国药理学通报》2008年第12期1579-1581,共3页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30060087)

摘　　要：目的研究萘哌地尔(naftopidil,Naf)对去甲肾上腺素(noradrenalin,NA)诱导大鼠血管平滑肌细胞(vascular smooth muscle cells,VSMCs)增殖的影响并探讨其机制。方法培养的VSMCs经NA诱导其增殖,分别用MTT比色法和细胞计数法检测Naf对VSMCs增殖的影响;荧光法测定细胞内钙浓度([Ca2+]i)及Real-TimeRT-PCR检测c-myc、c-fos、高血压相关基因(hypertension related gene-1,HRG-1)mRNA的表达。结果萘哌地尔(10-7～10-6mol·L-1)能够抑制NA诱导的VSMCs增殖,并明显降低VSMCs[Ca2+]i,降低c-myc、c-fos mRNA表达,增加HRG-1 mRNA的表达。结论萘哌地尔明显抑制NA诱导的VSMCs增殖,作用机制可能与其降低VSMCs[Ca2+]i、拮抗NA上调c-myc、c-fos mRNA的表达和拮抗NA下调HRG-1 mRNA的表达有关。Aim To study the effect of naftopidil （Naf） on noradrenalin （ NA ） -induced proliferation of rats vascular smooth muscle cells （VSMCs）, and explore its mechanisms. Methods The cultured VSMCs was induced to proliferate by NA, and effects of Naf on the VSMCs proliferation was tested by MTT assay and cell counting method respectively. The intra-cellular calcium concentration is investigated by fluorimetry, and the expressions of c-mye, c-los and hypertension related gene-1 （ HRG-1 ） mRNA were tested by Real- Time RT-PCR. Results The proliferation of VSMCs induced by NA was inhibited by Naf（ 10^-7 - 10^-6 mol·L^-1）, which diminished clearly VSMCs [ Ca^2＋ ]i and decreased mRNA expressions of c-myc, c-fos and increased the expression of HRG-1 mRNA. Conclusions Proliferation of VSMCs induced by NA can be inhibited clearly by Naf. The mechanisms may be related to diminishing [ Ca^2＋] i, antagonizing the up-regulation of c-myc and c-fos mRNA expressions by NA and antagonizing the down-regulation of HRG-1 mRNA expression.

关 键 词：萘哌地尔 血管平滑肌细胞 去甲肾上腺素 增殖 

分 类 号：R-322[医药卫生] R322.12