球囊血管成形术后纤溶酶原激活物抑制剂-1基因的表达与西拉普利的作用  

Changes of fibrinolytic activity and expression of PAI-1 gene after balloon injury in rabbits and effort of Cilazapril

作　　者：陈晓文[1] 戚文航[1] 

机构地区：[1]上海第二医科大学附属瑞金医院心内科,200025

出　　处：《中华心血管病杂志》2003年第3期220-222,共3页Chinese Journal of Cardiology

摘　　要：目的　通过建立兔再狭窄模型 ,系统观察了球囊血管成形术后血浆纤溶酶原激活物抑制剂 1(PAI 1)活性的变化 ,PAI 1基因表达情况 ,以了解PAI 1基因表达与再狭窄间关系。同时观察血管紧张素转换酶抑制剂————西拉普利对局部血管壁内PAI 1基因表达的影响。方法　对模型兔进行球囊血管成形术分别于术前、术后 3h、术后 1周、2周和 4周应用发色底物法测定血浆PAI 1活性 ,并利用RT PCR技术测定不同时期局部血管壁内PAI 1mRNA表达情况。另取再狭窄模型兔 16只 ,随机分为对照组 8只 ,西拉普利组 (治疗组 ) 8只。治疗组于术前 3d给药 ,剂量为 3mg·kg-1·d-1。术前、术后各时点测血浆PAI 1活性。于术后 4周处死动物 ,分离血管作病理形态学观察和计算机图像分析 ,应用RT PCR技术观察西拉普利对局部血管壁内PAI 1mRNA表达的影响。结果　血管成形术后 3h ,血浆PAI 1活性升高 ,术后 1周达高峰 ,于术后 4周降至术前水平 ;血管局部PAI 1mRNA在术前就有少量表达 ,术后 1d明显增加达高峰 ,术后 4周恢复术前水平。西拉普利可降低血浆PAI 1活性 ,对血管壁局部PAI 1基因表达 ,血管内膜、中膜的增生反应均有抑制作用 (P <0 0 1)。结论　本结果提示血管成形术后 ,局部PAI 1表达增加 ,可刺激局部血管平滑肌增生 ,并通过抑制?Objective To demonstrate a possible association between changes in the fibrinolytic potential and restenosis by using the balloon-injured rabbit model, to observe the changes of plasma plasminogen activator inhibitor type 1 (PAI-1) activity and the expression of PAI-1 gene in the arterial wall after vessel injury, and to test the role of cilazapril in vivo on the regulation of fibrinolytic activity and PAI-1 expression in arterial wall after endothelial injury. Methods In rabbit model subjected to balloon injury, plasma PAI-1 activity was determined by chromogenic assay; PAI-1 messenger ribonucleic acid (mRNA)expression was assayed with the use of RT-PCR. Cilazapril (3 mg·kg -1 ·d -1 p.o.n=8) were given 3 days before injury until sacrifice. Results PAI-1 activity in plasma increased significantly at 3h after vessel injury, which reached a peak of 26.18±3.69AU/ml one week after injury. The expression of PAI-1 mRNA was detectable slightly before injury,which increased significantly 3.4-fold within 1day after injury compared with that in control arteries. In cilazapril-treated group, compared with control rabbits, both PAI-1 activity and neointima and media proliferation decreased significantly (P<0.01), the induction of PAI-1 expression by balloon injury was significantly suppressed by 43%(P<0.01).Conclusion Our results indicated that balloon injury by angioplasty induced the increased intramural expression of PAI-1, stimulated vascular smooth muscle cell proliferation, resulted in the increased accumulation of extracellular matrix by the inhibition of regional fibrinolytic activity, which may contribute to restenosis. And cilazapril may interfere vessel proliferation through suppression of expression of PAI-1 in balloon-injured artery.

关 键 词：球囊血管成形术 纤溶酶原激活物抑制剂-1 基因表达 西拉普利 PAI-1 动物模型 

分 类 号：R54[医药卫生—心血管疾病]