萘哌地尔衍生物YMⅢ对血管紧张素Ⅱ诱导大鼠胸主动脉平滑肌细胞增殖的抑制作用  

Inhibition of Naftopidil Ramification YMⅢ on Cultured Thoracic Aorta Smooth Muscle Cells Proliferation of Rats Induced by Angiotensin Ⅱ

作　　者：杨征[1,2] 邱敏[1,3] 吴芹[1] 黄燮南[1] 

机构地区：[1]遵义医学院药理学教研室,贵州省遵义市563003 [2]包头医学院第一附属医院心内二科,内蒙古包头市014010 [3]包头医学院药学系,内蒙古包头市014010

出　　处：《中国动脉硬化杂志》2009年第9期727-730,共4页Chinese Journal of Arteriosclerosis

摘　　要：目的研究萘哌地尔衍生物YMⅢ对血管紧张素Ⅱ诱导Wistar大鼠和自发性高血压大鼠胸主动脉平滑肌细胞增殖的抑制作用及机制。方法将Wistar大鼠和自发性高血压大鼠胸主动脉平滑肌细胞进行体外培养，采用四甲基偶氮唑盐比色法检测YMⅢ对胸主动脉平滑肌细胞和血管紧张素Ⅱ诱导胸主动脉平滑肌细胞增殖的影响；用实时逆转录聚合酶链反应技术检测血管紧张素原、c—myc mRNA表达。结果未经血管紧张素Ⅱ处理的胸主动脉平滑肌细胞，0．1μmol／LYMⅢ能抑制Wistar大鼠和自发性高血压大鼠胸主动脉平滑肌细胞增殖；YMⅢ（0．01、0．05、0．1μmol／L）能呈浓度依赖性抑制血管紧张素Ⅱ所致Wistar大鼠和自发性高血压大鼠胸主动脉平滑肌细胞的增殖；YMⅢ（0．05～0．1μmol／L）作用能使血管紧张素Ⅱ所致Wistar大鼠血管紧张素原、c-myc mRNA表达水平下调，而各浓度YMⅢ均能下调血管紧张素Ⅱ所致自发性高血压大鼠胸主动脉平滑肌细胞的血管紧张素原、c-myc mRNA表达。结论YMⅢ明显抑制血管紧张素Ⅱ诱导大鼠胸主动脉平滑肌细胞的增殖，且抑制增殖作用在自发性高血压大鼠比在Wistar大鼠明显，其作用机制可能与下调血管紧张素原、c-myc mRNA的表达有关。Aim To investigate the inhibition of naftopidil ramification YM Ⅲ on Wistar rat and spontaneously hypertensive rat （ SHR） thoracic aorta smooth muscle cell （ tASMC ） proliferation induced by angiotensin Ⅱ （ Ang Ⅱ ）, and to explore the possible mechanisms. Methods Primary culture of tASMC from Wistar rat and SHR was established in vitro, and the effects of YM Ⅲ on tASMC proliferation induced by Ang Ⅱ were determined by methyl thiazolyl tetrazolium （MTT） assay. The effects of YM Ⅲ on the expressions of angiotensinogen （ AGT ） and c-myc mRNA were detected by real-time reverse transcription polymerase chain reaction （RT-PCR）. Results 0.1 μmol/L YM Ⅲ depressed Wistar rat and SHR tASMC proiferation and YMⅢ （0.01,0.05,0. 1μmol/L） depressed tASMC proiferation induced by AngⅡ in a concentration-dependent manner. YM Ⅲ （0.05 - 0.1 μmol/L） down-regulated the expression of AGT and c-myc mRNA on Wistar rat in 24 hours. YM Ⅲ （0.01,0.05,0.1 μmol/L ） down-regulated the expression of AGT and c-myc mRNA on SHR in 24 hours. Conclusions Proliferation of tASMC induced by Ang Ⅱ can be inhibited dearly by YM Ⅲ, the effect is more siguiticant on SHR than on Wistar rat. The mechanisms may be related to down-regulating the expression of AGT and c-myc mRNA.

关 键 词：萘哌地尔 动脉平滑肌细胞 血管紧张素Ⅱ 

分 类 号：R454.1[医药卫生—治疗学] R544.1[医药卫生—临床医学]