罗格列酮对血管球囊损伤后新生内膜增生及c-Fos和p27^(kip1)表达的影响  

Effects of rosiglitazone on neointimal hyperplasia and the expression of c-Fos and p27^(kip1) in rat carotid arteries after balloon injure

作　　者：周晓莉[1] 雷寒[1] 

机构地区：[1]重庆医科大学附属第一医院心内科,重庆400016

出　　处：《重庆医科大学学报》2011年第8期924-928,共5页Journal of Chongqing Medical University

摘　　要：目的:探讨PPARγ配体罗格列酮对大鼠颈总动脉球囊损伤后新生内膜增生及细胞增殖相关因子c-Fos和p27kip1表达的影响。方法:实验分为给药组[罗格列酮3 mg/(kg.d)]和对照组[生理盐水3 mg/(kg.d)],应用球囊血管内膜剥脱法建立大鼠颈总动脉再狭窄模型,苏木素-伊红染色检测术后不同时间点血管内膜与中膜的厚度比值(Intima/media,I/M)和面积比值(Inti-ma area/media area,IA/MA),比较2组血管新生内膜增生差别。分别应用RT-PCR和Western blot方法检测球囊损伤后不同时间点血管组织中c-Fos和p27kip1的mRNA和蛋白质的表达,比较在同一时间点两组间的表达差别。结果:罗格列酮能够抑制球囊损伤后血管新生内膜增生,罗格列酮组与对照组相比,在所有对应时间点上I/M及IA/MA均显著减少(P<0.000 1)。正常血管中c-Fos的表达很少,球囊损伤后表达增加,7 d后达高峰,14 d后下降。罗格列酮组与对照组相比,在所有时间点上均能显著抑制c-Fos的mRNA和蛋白质的表达(P<0.000 1)。正常血管中存在p27kip1的基础表达,球囊损伤后表达下调,7 d后降至最低点,14 d后回升。罗格列酮组与对照组相比,在所有时间点上均能显著上调p27kip1的mRNA和蛋白质的表达(P<0.000 1)。结论:罗格列酮可以显著抑制球囊损伤后血管新生内膜增生,其机制与调控细胞增殖相关因子c-Fos和p27kip1的转录表达有关。Objective：To investigate the effect of PPARγ ligand rosiglitazone on neointimal hyperplasia and the expression of c-Fos and p27kip1 in rat carotid arteries after balloon injure.Methods：Vascular restenosis in rat carotid arteries was established by balloon denudation.The thickness and area ratios of intima to media（I/M and IA/MA） were measured by using hematoxylin and eosin stain at different time after balloon injury.The mRNA levels and protein expression of c-Fos and p27kip1 in vascular tissues were measured by RT-PCR and Western blot,respectively.Results：Both I/M and IA/MA were significantly reduced in rosiglitazone treatment group [3 mg/（kg·d）] compared to that in control group treated with saline [3 mg/（kg·d）]（P0.000 1,n=5）.Although barely detectable in normal arteries,the mRNA and protein expression of c-Fos were increased one day after balloon injury.The increases of c-Fos reached peak levels on day 7 and declined after 14 days.Rosiglitazone markedly suppressed the mRNA and protein expression of c-Fos in arteries induced by balloon injury.In contrast to c-Fos,the expression of p27kip1 in arteries was decreased after balloon injury.The lowest level of p27kip1 were seen on day 7 after balloon injury and gradually recovered from day 14.The mRNA and protein expression of p27kip1 were significantly increased in rosiglitazone treatment group compared that in control group.Conclusion：These studies demonstrate that rosiglitazone inhibit neointimal hyperplasia in carotid arteries after balloon injury.Our results suggest that rosiglitazone suppresses neointimal hyperplasia by modulating c-Fos and p27kip1 expression.

关 键 词：罗格列酮 PPARγ C-FOS P27KIP1 新生内膜 

分 类 号：R541.4[医药卫生—心血管疾病]