硒对DEHP染毒小鼠学习记忆能力及PI3K/AKT/GSK-3β信号通路的影响  

Effects of selenium on learning and memory ability andPI3K/AKT/GSK-3βsignaling pathway in mice exposed to DEHP

作　　者：赵晨晨 田原瑗 姜勃宇 许妍姬[1] Zhao Chen-chen;TIAN Yuan-yuan;JIANG Bo-yu;XU Yan-ji(Department of Preventive Medicine,Yanbian University Medical School,Yanji,Jilin 133000,China)

机构地区：[1]延边大学医学院预防医学教研室,吉林延吉133000

出　　处：《现代预防医学》2023年第10期1876-1883,共8页Modern Preventive Medicine

基　　金：吉林省教育厅科学技术研究项目(JJKH20200532KJ);吉林省科技厅项目(YDZJ202201ZYTS158)。

摘　　要：目的研究硒(selenium,Se)对邻苯二甲酸二乙基己酯(diethylhexyl phthalate,DEHP)染毒小鼠学习记忆能力及磷脂酰肌醇3-激酶/蛋白激酶B/糖原合成酶激酶-3β(phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase-3β,PI3K/AKT/GSK-3β)信号通路的影响。方法选用雄性昆明种小鼠80只,体重为(20±2)g,随机分为正常对照(CT)组、低、中、高浓度DEHP组、Se组、低、中、高DEHP+Se组,共8组,每组10只。连续灌胃6周然后进行Morris水迷宫、避暗、跳台等行为学实验;再测定脑组织中CAT、SOD、GSH、AChE的活性和MDA的含量;ELISA检测脑组织中5-HT的含量;Western Blot检测PI3K/AKT/GSK-3β通路和凋亡相关蛋白表达水平;HE染色评估小鼠海马CA1区神经元的形态学变化。采用单因素方差分析LSD法比较相关数据的差异性。结果与CT组相比,DEHP染毒组小鼠寻找平台时间延长、目标象限停留时间和穿台次数减少(P<0.05),避暗、跳台潜伏期缩短、错误次数增加(P<0.05);小鼠脑组织中CAT、SOD、GSH活性和5-HT含量降低,MDA含量和AChE活性增加(P<0.05);PI3K、p-AKt/AKt、p-GSK-3β/GSK-3β、Bcl-2/Bax蛋白表达水平降低,Caspase-3蛋白表达水平增高(P<0.05);小鼠海马CA1区细胞排列无序、形态不完整,出现神经元丢失情况;DEHP+Se联合作用组与同等剂量DEHP组相比,学习记忆能力改善,生化指标活性增加,蛋白表达水平增高,海马CA1区细胞形态明显改善。结论Se干预DEHP对成年小鼠染毒引起的神经毒性,其机制可能是通过调节脑组织氧化应激水平和神经递质含量、激活PI3K/AKT/GSK-3β信号通路相关蛋白表达水平,拮抗神经细胞凋亡,从而改善染毒小鼠学习记忆障碍。Objective To investigate the effects of selenium(Se)on learning and memory ability and the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase-3β(PI3K/AKT/GSK-3β)signaling pathway in mice exposed to diethylhexyl phthalate(DEHP).Methods A total of 80 male Kunming mice with the body weight of(20±2)g were randomly divided into 8 groups with 10 mice in each group,including normal control(CT)group,low,medium and high concentration DEHP group,Se group,and low,medium and high DEHP+Se group.After continuous intragastric administration for 6 weeks,behavioral experiments such as Morris water maze,dark avoidance and platform jumping were conducted.The activity of CAT,SOD,GSH and AChE and the content of MDA in brain tissue were measured.The content of 5-HT in brain tissue was determined by ELISA.The expression levels of PI3K/AKT/GSK-3βpathway and apoptosis-related proteins were detected by Western Blot.HE staining was used to evaluate the morphological changes of neurons in the CA1 region of the hippocampus in mice.Single factor analysis of variance LSD was used to compare the differences of relevant data.Results Compared with CT group,mice in DEHP group the time to find the platform was prolonged,the time to stay in the target quadrant and the times of crossing the platform were reduced(P<0.05.The latent period of dark avoidance,platform jumping experiment was shortened and the number of errors was increased(P<0.05).The activities of CAT,SOD,GSH and 5-HT were decreased,while the contents of MDA and AChE were increased(P<0.05),and the protein expression levels of PI3K,Ph-Akt/Akt,Ph-GSK-3β/GSK-3β,Bcl-2/Bax decreased,the expression level of Caspase-3 protein increased(P<0.05).The arrangement of cells in CA1 area of hippocampus was disordered,the morphology was incomplete,and the neurons were lost.Compared with the same dose DEHP group,the ability of learning and memory was improved,the activity of biochemical indexes was increased,the level of protein expression was increased,and the cell morphology of hi

关 键 词：硒 DEHP 学习记忆 PI3K/AKT/GSK-3β信号通路 神经保护 

分 类 号：R114[医药卫生—卫生毒理学]