高脂饮食对载脂蛋白E基因敲除小鼠海马CA_3区形态学变化及mortalin蛋白表达的影响

摘要

Objective To investigate the effect of apolipoprotein E gene knock-out(ApoE KO) and high-fat diet on morphology and the expression of mortalin in hippocampal CA_3 neurons of mice, and to explore the impact of these factors on memory and Alzheimer's disease.Methods Ten wild-type and 10 ApoE KO mice were fed with common chow as the control group and the KO group respectively while 10 ApoE KO mice were fed with high fat diet.Twelve weeks later, the weight and the lid of these mice were measured.The brain tissues were observed using HE staining, nissl staining, protargol staining,immunohistochemistry staining and image analysis by computer.Results In the ApoE KO group, weight,total cholesterol, triglyceride, low-density lipoprotein cholesterol were higher than those in the control group,and these changes were more significant in ApoE KO high-fat diet group.The nissl was higher in the ApoE KO group (0.301±0.031) and in ApoE KO high-fat diet group (0.261±0.020) than those in the control group (0.341±0.035, F=18.068, P<0.05).The mortalin in the ApoE KO group (0.322±0.060) and in ApoE KO high-fat diet group (0.391±0.041) were higher than the control group (0.256±0.061, F=15.230, P < 0.05).Conclusions ApoE KO and high-fat diet can reduce nissl, and improve the expression of mortalin.This protein may be involved in the pathogenesis of Alzheimer's disease.%目的 观察载脂蛋白E(apolipoprotein E,ApoE)基因敲除(knock-out,KO)及高脂饮食后小鼠海马CA_3区形态学及mortalin蛋白表达的变化,以探讨这些因素与记忆损伤及阿尔茨海默病的关系.方法 10只野生型小鼠予普通饲料喂养作为对照(C)组,10只ApoE KO小鼠予普通饲料喂养作为KO组,10只ApoE KO小鼠予高脂饲料喂养作为KO-HF组.小鼠3个月龄成模后,称重;取血检测血脂;取小鼠脑组织分别进行HE染色、尼氏染色、神经原纤维银染、免疫组织化学染色和计算机图像分析.结果 KO组体质鼍、总胆固醇、甘油三酯及低密度脂蛋白胆固醇含量与C组相比明显升高,KO-HF组升高更明显;KO组(0.301±0.031)及KO-HF组(0.261±0.020)尼氏体较C组(0.341±0.035)减少(F=18.068,P<0.05);KO组(0.322±0.060)及KO-HF组(0.391±0.041)mortalin表达较C组(0.256±0.061)升高(F=15.230,P<0.05);KO组及KO-HF组未见明显神经原纤维缠结.结论 ApoE KO及高脂饮食可致小鼠海马CA,区锥体细胞内尼氏体减少,mortalin表达升高,该蛋白的异常表达可能与阿尔茨海默病的发病相关.