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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 observe the change of myocardial cells and myocardial interstitial components of ApoE - deficient (ApoE - / -) mice fed with high cholesterol, and to observe the effect of simvastatin. Methods: Thirty-six 8-week-old male ApoE - / - mice were fed high cholesterol diet for 8 weeks to 16 weeks and were randomly divided into three groups and continued to 24 weeks, 32 weeks and 40 weeks The rats in each week age group were divided into six groups (n = 6): model group (n = 6) and simvastatin intervention group (n = 6). C57BL / 6J mice of the same age were used as controls. Mice were sacrificed at the end of 24 weeks, 32 weeks and 40 weeks respectively. Cholesterol levels were routinely measured, and fresh total heart tissue was collected for determination of total cholesterol, nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA); cardiac tissue was fixed and paraffin sections were taken for HE staining Changes of myocardial cells in each group, Masson staining changes in myocardial collagen. Results: The levels of cholesterol and MDA in plasma and heart tissue of ApoE - / - mice at 24, 32 and 40 weeks old increased gradually (p <0.05), while the levels of NO and SOD decreased (p <0.05) Collagen content increased gradually (p <0.05). Compared with the model group at the same age, the levels of cholesterol and MDA in plasma and heart tissue of Simvastatin group were significantly decreased (p <0.05), and the diameters of myocardial cells were significantly decreased. The mean LV wall thickness of simvastatin group at 40 weeks (P <0.05). The levels of myocardial collagen in simvastatin group at 32 weeks and 40 weeks decreased significantly (p <0.05). CONCLUSION: ApoE-deficient mice fed high cholesterol are associated with increased cholesterol levels, reduced antioxidant capacity, increased cardiomyocyte diameter and myocardial collagen content, and simvastatin may reduce cardiac remodeling.