丙丁酚对兔经皮腔内血管成形术后内膜增生和细胞周期蛋白表达的抑制作用  

Inhibiting effect of probucol on neointimal hyperplasia and expression of related cell cycle proteins after percutaneous transluminal angioplasty in rabbits

作　　者：涂永生[1] 杨云波[1] 廖端芳[1] 

机构地区：[1]湖南南华大学药物药理研究所,湖南衡阳421001

出　　处：《中国心血管杂志》2003年第1期1-3,14,共4页Chinese Journal of Cardiovascular Medicine

基　　金：国家自然科学基金 (编号 :39970 847);湖南省自然科学基金 (编号 :99JY2 0 0 32 )项目

摘　　要：目的　研究丙丁酚对兔经皮腔内血管成形术 (PTA)后内膜增生及管壁细胞周期蛋白表达的影响。方法　新西兰白兔随机分为假手术对照组 ,PTA术后 2周组及 PTA术加丙丁酚防治 3周组和 5周组。治疗组在 PTA术前1周给药 ,术后继续给药 2周和 4周 ,分别为丙丁酚防治 3周组和 5周组。取各组实验动脉段石蜡切片 ,采用计算机图象分析系统分别测出中膜面积 (MA)、新生内膜面积 (NEA) ,并计算新生内膜面积与中膜面积的比率 (NEA /MA)。用免疫组化测周期素 D1 (cyclin D1 )、周期素依赖激酶 4(cyclin- dependent kinase 4,cdk4)及增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达水平。结果　 PTA术后 2周组 ,内膜增生显著 ,cdk4、cyclin D1 和PCNA均在内膜层表达 ,而中膜表达较少或几乎检测不到。与 PTA术后 2周组相比 ,丙丁酚防治 3周组新生内膜减少达 71.3 % (P<0 .0 1) ,cdk4、cyclin D1 和 PCNA阳性表达指数分别低 69.9%、73 .7%和 79.6% (P均 <0 .0 1)。结论　丙丁酚防治 3周对兔血管损伤后内膜增生抑制作用显著 ,同时伴有 cdk4、cyclin D1 和 PCNA阳性表达下降。Objective To investigate the effect of probucol on neointimal hyperplasia and expression of related cell cycle proteins after percutaneous transluminal angioplasty (PTA) in rabbits. Methods Rabbits were randomly assigned to a sham operation group, PTA 2 weeks group,PTA plus probucol 3 weeks group and probucol 5 weeks group. Probucol was given orally 1g/d from 1 week prior to PTA to the time of killing(2 or 4 weeks after PTA, that's probucol 3 weeks group and probucol 5 weeks group respectively).Then the medial area (MA), neointimal area(NEA) and neointimal area(NEA)/medial area(MA) were analyzed by computerized digitizer system. The expression of cyclin dependent kinase4(cdk4) , cyclin D 1 and proliferating cell nuclear antigen(PCNA) were measured by immunohistochemical technique and computer image analyzer. Results In PTA 2 weeks group ,cdk4, cyclin D 1 and PCNA expressed mainly in the neointima but with low or undetected expression in the media,the expression of cdk4,cyclin D 1 and PCNA increased with the intimal thickening.Compared with PTA 2 weeks group, the neointimal area reduced by 71.3%( P <0.01),and the positive expression indexes of cdk4, cyclin D 1 and PCNA decreased by 69.9%, 73.7% and 79.6% respectively (all P <0.01) in PTA plus probucol 3 weeks group. Conclusion Probucol can effectively inhibit neointimal thickening after angioplasty,which is probably due to decrease in the expression of cdk4, cyclin D 1 and PCNA.

关 键 词：丙丁酚 新生内膜 细胞周期调节蛋白 血管成形术 再狭窄 

分 类 号：R965[医药卫生—药理学]