辛伐他汀对支架置入后兔腹主动脉内膜增生的影响  

Effect of simvastatin on intimal proliferation in abdominal aorta of rabbits after stenting

作　　者：许文克[1] 高传玉[2] 于洁[2] 

机构地区：[1]郑州大学第一附属医院心内科,郑州市河南省人民医院450052 [2]河南省人民医院心内科

出　　处：《中国介入心脏病学杂志》2008年第2期103-107,共5页Chinese Journal of Interventional Cardiology

摘　　要：目的观察辛伐他汀对兔腹主动脉支架置入后内膜增殖的影响。方法30只新西兰大白兔随机分为对照组和辛伐他汀治疗组。采用含1.5%胆固醇的高脂饮食加腹主动脉内皮剥脱术制作兔腹主动脉粥样硬化模型。内皮剥脱术后第12周实验组和对照组服用阿司匹林25mg/d,氯吡格雷12.5mg/d,3d后,分别行支架置入术。术后实验组继续服用辛伐他汀5mg/d,服药至第30天处死动物,取腹主动脉含支架段血管,进行血管壁组织形态学变化观察和检测细胞周期抑制蛋白P27kip1、增殖细胞核抗原(PCNA)在各组的表达量的变化。结果血管超声发现内皮剥脱术后第10周实验组和对照组腹主动脉均可见有不同程度的粥样硬化斑块和血管内狭窄。组织形态学观察发现服用辛伐他汀的实验组兔腹主动脉支架段内的血管内膜厚度(0.107±0.072mm,与对照组0.133±0.047mm比,P=0.006)、新生内膜面积(0.975±0.084mm2,与对照组1.350±0.043mm2比,P=0.001)均明显降低,且血管的狭窄程度较轻(20.460%±2.325%,与对照组31.020%±1.904%比,P=0.002)。实验组兔腹主动脉支架段内的血管新生内膜中的血管平滑肌细胞(VSMC)的胞核P27kipl蛋白表达量明显升高(7.149±0.305,与对照组2.997±0.310比,t=9.551,P<0.05),而血管新生内膜中VSMC的胞核PCNA表达量明显降低(着色强度IS为3.003±0.192,与对照组着色强度IS5.268±0.475比,t=4.423,P<0.05)。结论辛伐他汀能明显抑制支架置入术后血管内膜增生。其机制可能为通过上调P27kip1蛋白表达量,使增殖标志物PCNA表达量降低,而对VSMC增殖周期起负调控作用,达到抑制VSMC增殖和新生内膜的增生。Objective To observe the effect of simvastatin on intimal proliferation in abdominal aorta of rabbits after stenting. Methods Thirty male New Zealand white rabbits were allocated into two groups including the control group （ n = 15 ） and the treatment group （ n = 15 ）. All the rabbits were fed on 1.5% high cholesterol diet and underwent ballon injury of abdominal aorta from femoral approach and stents were implanted in the segments with stenosis rate greater than 50%. Rabbits in the treatment group were given simvastatin 5 mg/d after stenting. Neointima proliferation of the stented segments was examined on the 30th day after stenting by histological staining and the expression of P^27kipl and PCNA in each group was also analyzed. Results Histological staining showed that on the 30^th day after stenting, the thickness of vessel wall （ 0. 107 ± 0. 072 mm vs 0.133± 0. 047 mm, P = 0. 006） and the area of neointima （ 0. 975 ± 0. 084 mm^2 vs 1. 350 ± 0. 043 mm^2, P = 0. 001 ） were less in the simvastatin treatment group compared with the control and the rate of lumen loss was less than that of the control （20. 460% ±2. 325% vs 31. 020%± 1. 904%, P =0. 002）. The expression of p27kipl in the neointima VSMC cell nuclear was higher （7. 149 ± 0. 305 vs 2. 997 ± 0. 310, t = 9. 551, P 〈 0. 05） but the expression of PCNA was less in the treatment group compared with the control （IS： 3.003 ±0. 192 vs 5.268±0.475, t =4.423,P〈0.05）. Conclusion Simvastatin could reduce the thickness of hyperplastic neointima and the degree of stenosis in the stented aorta. The mechanism involved may be related to the up-regulation of P^27kipl protein expression and the down-regulation of PCNA expression in the neointima VSMC cell nuclear.

关 键 词：动脉粥样硬化 支架 辛伐他汀 细胞周期蛋白质类 增殖细胞核抗原 

分 类 号：R589.2[医药卫生—内分泌] R654.3[医药卫生—内科学]