ApoE基因缺陷小鼠的心肌肥厚及辛伐他汀的干预研究

Effects of Simvastatin on Myocardial Hypertrophy in Apolipoprotein E-Konckout Mice

目的:观察高胆固醇喂养的不同周龄ApoE基因缺陷(ApoE-/-)小鼠心肌细胞和心肌间质成分的改变,并观察辛伐他汀对其的影响。方法:36只8周龄雄性ApoE-/-小鼠饲以高胆固醇饲料喂养8周即至16周龄,随机被分为三组继续喂养至24周龄组、32周龄组和40周龄组,每一周龄组为12只,再随机分为模型组6只和辛伐他汀干预组6只(25mg/kg/d),相同周龄的C57BL/6J小鼠设为对照。分别在24周、32周、40周结束时处死小鼠。常规检测血浆胆固醇水平,留取新鲜心脏组织测定总胆固醇及一氧化氮(NO)、超氧化物歧化酶(SOD)、丙二醛(MDA);另取心脏组织固定,石蜡切片,HE染色观察各组小鼠心肌细胞的变化,Masson染色观察心肌胶原改变。结果:24、32和40周龄模型组ApoE-/-小鼠血浆、心脏组织胆固醇和MDA水平逐渐增加(p<0.05),NO和SOD水平逐渐降低(p<0.05),心肌细胞直径和心肌胶原含量逐渐增加(p<0.05)。与相同周龄模型组相比,辛伐他汀干预组血浆、心脏组织胆固醇和MDA水平明显降低(p<0.05),心肌细胞直径明显减小;40周龄辛伐他汀干预组左室壁平均厚度明显降低(p<0.05),32周龄和40周龄辛伐他汀干预组心肌胶原含量明显减少(p<0.05)。结论:高胆固醇喂养的ApoE基因缺陷小鼠,随着周龄增加、胆固醇水平增加,抗氧化能力降低,心肌细胞直径和心肌胶原含量显著增加,辛伐他汀可能减轻心脏重构。

Objective： To study the changes in myocardial cells and myocardial collagen in apoE-deficienct （apoE-/-） mice of dif- ferent weeks in cholesterol-fed manner, and to investigate the effects of Simvastatin on it. Methods： Thirty six male apoE-deficienct mice at the age of eight weeks were fed in high cholesterol untill 16 weeks, and then were fed and randomized into three groups： twen- ty-four-week group （n=12）, thirty-two-week group （n=12）, forty-week group （n-12）. Each group was randomized again into two groups： model group （n=6） and simvastatin intervention group （n=6）. Normal C57BL/6J mice were set as the control group. Serum cholesterol, low-density lipoprotein cholesterol （LDL-C）, triglyceride, high-density lipoprotein cholesterol （HDL-C） concentrations were determined. Opticalmicroscopy was adopted to assess the myocardial cells changes. In order to observe myocardial collagen with Masson dye, image analysis was performed with computer. Collagen specific dyeing and quantitative analysis were identified by Picric-Sirius Red Polarimetry. Results： The diameter of myocardial cells and the content of myocardial collagen of Apolipoprotein E-konckout mice were significantly increased in twenty-four-week model group, thirty-two-week model group and forty-week model group, while diameter of myocardial cells and the content of myocardial collagen were significantly decreased in simvastatin intervention group （P〈0.05）. Conclusions： Diameter of myocardial cells and the content of myocardial collagen were significantly increased in apoE-deficienct （apoE-/-） mice fed with cholesterol. Simvastatin may relieve cardiac remodeling.