高胆固醇对AD大鼠海马神经元缺失和Tau蛋白异常磷酸化的影响

目的 研究高胆固醇饮食对阿尔茨海默病(AD)大鼠海马神经元缺失和Tau(ser202)异常磷酸化的影响.方法 海马齿状同注射B淀粉样蛋白(A13)建立AD大鼠模型,根据不同饮食,将动物分为高胆同醇AD组、高胆同醇磷酸盐缓冲液(PBS)组、标准饮食AD组和标准饮食PBS组;采用尼氏染色方法检测海马神经元缺失率,应用免疫组织化学方法检测海马及皮层Tau(ser202)磷酸化水平.结果 高胆固醇饮食增加海马神经元缺失,高胆固醇饮食AD组海马神经元缺失率(30.9%±4.6%)明显大于标准饮食AD组(22.7%±1.9%)、高胆同醇饮食PBS组(7.O%±1.5%)和标准饮食PBS组(5.4%±1.1%),差异均有统计学意义(P＜0.05);高胆固醇AD组、标准饮食AD组、高胆固醇PBS组、标准饮食PBS组海马齿状回(Pser202)Tau阳性细胞数分别为65.5±6.2、48.8±4.8、22.5±3.1和12.7±1.7,比较差异均有统计学意义(P＜0,05).结论 高胆固醇饮食促进Aβ诱导神经元缺失和Tau蛋白异常磷酸化.

Effect of high-cholesterol diet on neuronal loss and Tau(ser202)phosphorylation in a rat model of Alzheimer's disease

Objective To study the effect of high-cholesterol diet on neuronal loss and Tau (set202)phosphorylation in a rat model of Alzheimer's disease(AD). Methods Twenty rats were randomized into high-cholesterol diet+AD group,standard diet+AD group,high-cholesterol diet+PBS group,and standard diet+PBS group.In the former two groups,amyloid-β peptide(Aβ1-40)was injected into the right dentate gyms of the hippocampus to establish experimenml AD,and PBS was injected instead in the latter two groups.Corresponding feed was administered in the 4 groups aS indicated.The hippocampal neuronal loss in the rats Was assessed using Nissel staining,and the level of Tau(ser202)phosphorylation was estimated with immunohistochemistry.Result The mts in cholesterol+AD group exhibited serious neuronal loss at the rate of 30.9%±4.6%.which was significantly higher than those in standard diet+AD group(22.7%±1.9%),cholesterol+PBS group(7.0%±1.5%),and standard diet+PBS group(5.4%±1.1%).The numbers of Tau-positive cells in the dentate gyrus in the 4 groups were 65.5± 6.2,48.8±4.8,22.5±3.1,and 12.7±1.7,respectively. Conclusion High cholesterol diet aggravates neuronal loss and enhances Tan(ser202)phosphorylation in the dentate gyrus in AD rats.