辛伐他汀对平滑肌增殖的影响和可能的分子机理  

Effect of simvastatin on vessel smooth muscle cell proliferation and possible mechanism after stenting in abdominal aorta of rabbits

作　　者：高传玉[1] 许文克[1] 于洁[1] 张连仲[1] 袁建军[1] 马业心[1] 

机构地区：[1]华中科技大学通济医学院同济医院心内科,武汉市430030

出　　处：《实用诊断与治疗杂志》2006年第1期5-7,10,共4页Journal of Practical Diagnosis and Therapy

摘　　要：目的:观察辛伐他汀对兔腹主动脉支架植入术后平滑肌增殖和和血管平滑肌(V SM C)中α—平滑肌肌动蛋白、P 27k ip1蛋白、增殖细胞核抗原PCNA表达量的变化。方法:45只健康的新西兰雄性大白兔随机分为正常组(n=15),给予正常饮食;对照组(n=15)和实验组(n=15),采用含1.5%胆固醇的高脂饮食加腹主动脉内皮剥脱术制造兔腹主动脉狭窄模型。内皮剥脱术后第10周实验组和对照组服用阿司匹林25 m g/d,氯吡格雷12.5 m g/d,3 d后,分别行支架植入术。术后实验组继续服用辛伐他汀5 m g/d,服药至第30 d处死动物,取腹主动脉含支架段血管,进行血管组织形态学变化观察和检测P 27k ip1蛋白、PCNA、α-平滑肌肌动蛋白在各组的表达量的变化。结果:血管造影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(P>0.05)。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膜厚度(P<0.01)、新生内膜面积(P<0.01)均明显降低,而残余管腔面积明显增大(P<0.01),且血管的狭窄程度较轻。W estern b lot结果显示:对照组腹主动脉α-平滑肌肌动蛋白的表达明显比正常组下降55.4%,辛伐他汀治疗组α-平滑肌肌动蛋白的表达比对照组进一步降低了约29.7%(P<0.05)。实验组兔腹主动脉支架段内的血管新生内膜中的V SM C的胞核P 27k ip1蛋白表达量明显升高(P<0.01),而血管新生内膜中V SM C的胞核PCNA表达量明显降低(P<0.01)。结论:辛伐他汀能明显抑制支架植入术后平滑肌细胞增殖,降低α-平滑肌肌动蛋白的表达,其机理可能与抑制平滑肌细胞DNA增殖周期的P 27k ip1蛋白表达量增加和促进DNA增殖标志物PCNA表达量降低有关。Objective To observe the effect of simvastatin on vessel smooth muscle cell proliferation and the changes of P27kipl express and proliferating cell nuclear antigen （PCNA） after stenting in abdominal aorta of rabbits. Methods Forty-five male New Zealand white rabbits were allocated into three groups： normal group （n = 15） was on normal diet; control group （n = 15） was on 1. 5% high cholesterol diet and underwent denudation injury of abdominal aorta with balloon from femoral approach and a stent was implanted at stenosis segment when more than 50% stenosis had formed angiographically; treatment group （n = 15） was given simvastatin 5 mg/d after stenting, and other treatments were the same as control group. Rabbits were killed on the 30th day after stenting, stented abdominal aorta and proliferated neointima in stent was harvested. The histological changes of abdominal aorta was observed; the expression of P27kipl , Smooth muscle cell α-actin and PCNA in each group was analyzed. Results （1） The histomorphologic results showed that the neointima was mainly composed of smooth muscle cells after stenting. There was a great difference of the thinkness of vessel wall of neointima and the neointimial area between the treatment group and control group; （2）The expression of α-actin in treating group was significantly decreased when comparing to normal group and control group; （3）Compared with control group, the expression of P27kipl in the neointima VSMC cell nuclear increased （P〈0.01）;and the expression of PCNA decreased（P〈0. 01）. Conclusion （1） The atherosclerosis and stenosis model with rabbits has been successfully established by balloon de-endotheliazation plus cholesterol diet; （2） The results of ultrasonic Doppler are accordant with angiography for the stenosis evaluation of abdominal aorta; （3） Simvastatin could decrease the expression of α-actin and the thickness of hyperplastic neointima; The mechanism involved in this process may be related with the increase

关 键 词：动脉粥样硬化 支架 辛伐他汀 A-平滑肌肌动蛋白 P27KIPL蛋白 增殖细胞核抗原 

分 类 号：R96[医药卫生—药理学]