卵巢切除对APP/PS1小鼠认知功能和海马雌激素受体表达的影响

Effect of ovariectomy on cognitive function and hippocampal estrogen receptor expression in APP/PS1 mice

目的 本研究旨在观察阿尔茨海默病(Alzheimer’s disease, AD)动物模型APP/PS1雌性小鼠卵巢切除(ovariectomized, ovx)术后海马组织中Aβ沉积和雌激素受体水平在不同月龄的变化规律。方法 将3月龄APP/PS1雌性小鼠分3组,每组20只,10只采用经腹手术切除双侧卵巢作为模型(ovx)组,10只摘除相应部位的等体积脂肪作为对照(sham)组。分别饲养3个月、4个月、5个月作为6月龄组、7月龄组、8月龄组,通过Morris水迷宫评价不同月龄APP/PS1小鼠认知功能,透射电镜观察两组小鼠海马CA1区细胞内细胞器形态变化,免疫荧光染色检测两组小鼠海马CA1区Aβ沉积,ELISA检测两组小鼠血清雌激素、ROS、SOD、MDA水平和含量,Western blot测定ERα和ERβ表达水平。结果 随着月龄的不断增加,水迷宫测试中ovx组小鼠逃避潜伏期逐渐延长,海马CA1区Aβ沉积增加、海马神经元线粒体肿胀增加,胞浆内见大量脂褐素及淀粉样沉积;血清雌二醇水平、SOD活力下降,ROS水平、MDA含量增加,海马组织ERα和ERβ表达降低。结论 小鼠卵巢切除术后可能会加剧海马Aβ沉积,其认知功能降低呈现年龄依赖性。

Objective The present study aimed to observe the changes in Aβdeposition and estrogen receptor levels in the hippocampal tissue of female APP/PS1 mice with Alzheimer's disease(AD)after receiving an ovariectomy at different ages.Methods 3-month-old APP/PS1 female mice were divided into three groups,with 20 mice in each group.Ten mice were treated with bilateral ovarian resection via abdominal surgery as the model(ovx)group.The 10 mice in the control(sham)group underwent surgery in which an equivalent volume fat was removed from the corresponding area.After 3,4,and 5 months,APP/PS1 mice were assigned to 6-,7-,and 8-month age groups.The cognitive function of the APP/PS1 mice of different ages was evaluated using the Morris water maze.Morphological changes to intracellular organelles in the CA1 area of the hippocampus of the two groups of mice were observed using transmission electron microscopy.Immunofluorescence staining was used to detect the deposition of Aβin the CA1 area of the hippocampus of the two groups of mice.ELISA was used to detect the levels and contents of serum estrogen,ROS,SOD,and MDA,and Western blot was used to determine the expression levels of ERαand ERβ.Results As the ovx group mice increased in age,their escape latency in the water maze test gradually lengthened,the deposition of Aβin the hippocampal CA1 area increased,the mitochondrial swelling of hippocampal neurons increased,and larger amounts of lipofuscin and amyloid deposition were observed in the cytoplasm.Their serum E_2 levels and SOD activity decreased,while their ROS levels and MDA contents increased,and the expression of ERαand ERβin the hippocampal tissue decreased.Conclusions Ovariectomy in mice with low estrogen status may exacerbate hippocampal Aβdeposition and age-dependent cognitive decline.