辛伐他汀消退老年载脂蛋白E基因敲除小鼠动脉粥样硬化斑块的观察

Effect of simvastatin therapy on regression of atherosclerotic plaque in old apoE gene-deleted mice

目的观察辛伐他汀对高脂喂养的老年载脂蛋白E(apoE)基因敲除小鼠动脉粥样硬化(AS)斑块的作用。方法选取高脂喂养的60周龄雄性aopE基因敲除小鼠30只,随机分为辛伐他汀高剂量组、辛伐他汀低剂量组和模型组,每组10只,分别每天予以辛伐他汀20mg/kg、辛伐他汀5mg/kg和等量生理盐水灌胃,连续灌胃8周后,取主动脉窦部做病理检测。冷冻切片光镜下观察AS斑块病理情况,免疫组织化学染色观察骨桥蛋白、α肌动蛋白的表达。vonkossa染色观察斑块钙化情况。结果与模型组比较,辛伐他汀高、低剂量组apoE基因敲除小鼠的血清TC和LDL-C水平明显降低(P<0.05),斑块面积占管腔面积比、斑块内钙化染色面积明显减少(P<0.05)。结论辛伐他汀可明显降低老年apoE基因敲除小鼠的血清TC和LDL-C水平,消退AS斑块的大小及其钙化。

Objective To investigate the effect of simvastatin on regression of atherosclerotic（AS） plaque in old apolipoprotein E gene（apoE）-deleted mice. Methods Thirty 60-week-old apoE-deleted mice exhibiting advanced atherosclerotic plaques were randomly divided into three groups： model group, high-dose simvastatin-treated group, and regular simvastatin-treated group. They were administered with saline, simvastatin 20 mg/kg per day, and simvastatin 5 mg/kg per day for 8 weeks respectively. After that,the mice were sacrificed for examination of serum lipids and aortic sinus was taken for pathological examination. Frozen slides of aorta were stained with hematoxylin and eosin, oil red O stain, histochemical stains for OPN and α-actin and von Kossa stain. Analysis was performed with a computerized image analysis program （Image Pro Plus）. Results Serum cholesterol levels were significantly decreased （P 〈0.05） and histological analysis of sections of aorta demonstrated a significant reduction in cross-sectional area of atherosclerotic lesions （P〈0.05） and the frequency of calcification in atherosclerotic plaques （P〈0. 01） in the simvastatin-treated mice compared with control mice. Conclusions The resuts indicated that serum cholesterol levels were significantly decreased in the simvastatin-treated mice compared with control mice. Simvastatin has anti-atherosclerotic effects on advanced atherosclerotic lesions.