锌对产前慢性应激致APP/PS1转基因子鼠学习能力损伤的影响及机制  

Effect and mechanism of zinc on learning ability impairment of APP/PS1 transgenic mice induced by prenatal chronic stress

作　　者：苏童 沈静[1] 宁丽[1] 陶宁[1] 李树林[2] 王茜[1] SU Tong;SHEN Jing;NING Li;TAO Ning;LI Shulin;WANG Qian(School of Public Health,Xinjiang Medical University,Urumqi Xinjiang,830011,China;Urumqi Center for Disease Control and Prevention,Urumgi Xinjiang,830000,China)

机构地区：[1]新疆医科大学公共卫生学院,新疆乌鲁木齐830011 [2]乌鲁木齐市疾病预防控制中心,新疆乌鲁木齐830000

出　　处：《职业与健康》2023年第20期2774-2777,共4页Occupation and Health

基　　金：新疆维吾尔自治区自然科学基金项目资助(2017D01C186)。

摘　　要：目的 了解锌的干预对产前慢性应激合并子代慢性应激的APP/PS1转基因小鼠学习能力的影响及其机制。方法 孕鼠在产前施加慢性应激后,从子代中选取32只APP/PS1转基因雄鼠,正常饲养至6月龄后,随机分成4组:加锌高、中、低剂量组(30.34、15.18、6.1 mg/kg)和空白对照组,每组8只,从6月龄开始进行3个月慢性应激的同时添加锌的干预,应激结束后使用Morris水迷宫实验检测学习记忆能力,通过苏木素-伊红(HE)染色观察小鼠海马CA3区域的病理情况,使用ELISA实验检测海马组织中Aβ1-40、Aβ1-42,Western blot实验检测海马组织BACE1的表达水平。结果 Morris水迷宫:与空白对照组相比,锌干预组的潜伏期时间更短;穿越平台的次数更多(均P<0.01);HE染色:空白对照组的海马CA3区结构紊乱,细胞坏死松散,锌干预组的神经细胞数量较多,状态较好,结构较清晰;ELISA实验与Western blot实验:与对照组相比,各剂量组Aβ1-40、Aβ1-42和BACE1的表达水平均降低(均P<0.05)。结论 补充一定的锌元素能够通过降低BACE1的生成,减少海马内Aβ1-40、Aβ1-42的表达量,从而改善产前慢性应激合并子代慢性应激对APP/PS1转基因小鼠海马的损伤以及学习记忆能力的影响。Objective To study the effect and mechanism of zinc intervention on the learning ability of APP/PS1 transgenic mice with prenatal chronic stress and offspring chronic stress. Methods After prenatal chronic stress,32 APP/PS1 transgenic male rats were selected from their offspring. After normal feeding to the age of six months,they were randomly divided into four groups:high,medium and low dose groups(30.34,15.18,6.1 mg/kg) and blank control group,eight rats in each group.From the age of six months,they were subjected to chronic stress for three months and zinc intervention was added at the same time. After the stress treatment,the Morris water maze test was used to test learning and memory ability,pathology of hippocampal CA3 region of mice was observed by hematoxylin eosin(HE) staining,Aβ1-40and Aβ1-42in hippocampus were detected by ELISA,and the expression level of BACE1 in hippocampus were detected by Western blot. Results Morris water maze:compared with the blank control group,the incubation period of zinc intervention group was shorter,and the number of crossing platforms was more(all P<0.01).HE staining:the structure of hippocampal CA3 area in the blank control group was disordered,the cells were necrotic and loose,and the number of nerve cells in the zinc intervention group was large,the state was good,and the structure was clear.ELISA experiment and Western blot experiment:compared with the control group,the expression levels of Aβ1-40,Aβ1-42and BACE1 in all dose groups decreased(all P<0.05). Conclusion The supplement of certain zinc can reduce the expression levels of Aβ1-40,Aβ1-42in hippocampus by decreasing the production of BACE1,so as to improve the damage of hippocampus and learning and memory ability of APP/PS1 transgenic mice caused by prenatal chronic stress combined with offspring chronic stress.

关 键 词：阿尔茨海默病 锌元素 APP/PS1转基因小鼠 学习能力 慢性应激 

分 类 号：R-332[医药卫生]