氟伐他汀抑制大鼠血管平滑肌细胞迁移的机制  

Fluvastatin inhibits migration of rat vascular smooth muscle cells

作　　者：陈海峰[1,2] 谢良地[1] 许昌声[1] 

机构地区：[1]福建医科大学附属第一医院高血压研究所,福建福州350005 [2]福建省立医院心内科,福建福州350001

出　　处：《中国病理生理杂志》2010年第8期1527-1531,共5页Chinese Journal of Pathophysiology

基　　金：福建省青年人才创新项目(No.2008F3026);福建省医学创新课题资助项目(No.2003-CX-12);福建医科大学科学研究发展基金资助项目(No.FJGXY04003)

摘　　要：目的:研究氟伐他汀抑制血管紧张素Ⅱ(AngⅡ)与血小板源性生长因子-BB(PDGF-BB)诱导的大鼠血管平滑肌细胞(VSMCs)迁移的可能机制。方法:采用体外培养大鼠胸主动脉平滑肌细胞;用特异性单克隆磷酸化热休克蛋白27(phospho-HSP27)抗体的Western blotting检测HSP27的活性;用FITC-鬼笔环肽标记F-actin并在激光共聚焦显微镜下观察细胞骨架的形态变化;采用改良的Boyden微孔膜双槽法进行细胞迁移实验。结果:AngⅡ和PDGF-BB呈浓度依赖性诱导VSMCs的HSP27磷酸化,使VSMCs内F-actin数量明显增加,纵向平行排列,形成应力纤维丝,并促进细胞迁移。100μmol/L HSP27阻断剂槲皮素可阻抑AngⅡ、PDGF-BB刺激VSMCs后产生的应力纤维丝形成,对AngⅡ、PDGF-BB诱导的VSMCs迁移的抑制率分别为55.3%和53.6%,P<0.01。氟伐他汀抑制AngⅡ和PDGF-BB诱导的HSP27磷酸化,并有量效关系,抑制作用在10-5mol/L时最显著,最大抑制率分别为42.1%和58.5%,P<0.01。结论:氟伐他汀可能通过抑制HSP27磷酸化影响VSMCs的迁移。AIM： To investigate the inhibitory effects of fluvastatin on the migration of rat vascular smooth muscle cells（VSMCs） induced by angiotensin II（AngⅡ） and platelet derived growth factor-BB（PDGF-BB）.METHODS： Cultured VSMCs derived from rat thoracic aorta were used.The activity of heat shock protein 27（HSP27） was evaluated by Western blotting with specific phospho-HSP27 antibody.The effect of F-actin polymerization was detected by FITC-phalloidine staining and examined by confocal microscopy.Modified Boyden chamber technique was employed for VSMCs migration assessment.RESULTS： The phosphorylation of HSP27 in VSMCs was increased by the stimulation of AngⅡ and PDGF-BB in a concentration-dependent manner.Treatment with AngⅡ and PDGF-BB resulted in a substantial increase in the number of stress fibers and rearrangement of these structures into ordered parallel arrays.The migration of VSMCs was promoted by AngⅡ and PDGF-BB.Reorganization of actin cytoskeleton stimulated with AngⅡ and PDGF-BB was inhibited by a specific HSP27 inhibitor quercetin（100 μmol/L） pretreatment.The inhibitory rates of 100 μmol/L quercetin on the migration of VSMCs induced by AngⅡ and PDGF-BB were 55.3% and 53.6%,respectively（P0.01）.The phosphorylation of HSP27 in response to AngⅡ and PDGF-BB was suppressed by fluvastatin in a dose-dependent manner,and maximal inhibitory rates were between 42.1% and 58.5% with 10-5 mol/L fluvastatin,respectively（P0.01）.CONCLUSION： Fluvastatin influences the migration of VSMCs in part by inhibiting HSP27 phosphorylation.

关 键 词：氟伐他汀 细胞迁移 热休克蛋白质27 肌 平滑 血管 

分 类 号：R363[医药卫生—病理学]