亚慢性铝染毒对大鼠海马CPEB3及突触可塑性的影响  

Effects of subchronic aluminum exposure on hippocampal CPEB3 and synaptic plasticity in rats

作　　者：纪晶晶 王艳妮 王国美 夏轶 徐义荣[1] 吴惠文[1] Jl Jingjing;WANG Yanni;WANG Guomei;XIA Yi;XU Yirong;WU Huiwen(Shanxi Medical University Fenyang College,Fenyang,Shanxi 032200,China;School of Public Health,Shanxi Medical University,Taiyuan,Shanxi 030001,China)

机构地区：[1]山西医科大学汾阳学院,山西汾阳032200 [2]山西医科大学公共卫生学院,山西太原030001

出　　处：《环境与职业医学》2021年第7期717-724,共8页Journal of Environmental and Occupational Medicine

基　　金：国家自然科学青年基金项目(81803208);山西省教育厅高等学校科技创新项目(2019L0997)。

摘　　要：[背景]铝的神经毒性表现为学习记忆能力受损,突触可塑性下降是铝致学习记忆受损的主要机制,但其分子机制并不清楚。[目的]探讨亚慢性染铝对大鼠海马多聚腺苷酸化元件结合蛋白3(CPEB3)以及突触可塑性的影响。[方法]取40只2月龄健康雄性SD大鼠,随机分为4组,分别为对照组、低剂量组(10μmol·kg^(-1))、中剂量组(20μmol·kg^(-1))和高剂量组(40μmol·kg^(-1))的麦芽酚铝染毒组,每组10只。腹腔注射染铝,每100 g体重染毒剂量为0.1 m L,对照组大鼠给予等体积0.9%氯化钠溶液,隔天染铝,持续3个月。采用Morris水迷宫检测大鼠的学习记忆能力,Western blotting法检测CPEB3、突触后致密蛋白95(PSD95)、离子型谷氨酸受体1(Glu R1)、离子型谷氨酸受体2(Glu R2)、环磷腺苷效应元件结合蛋白(CREB)和脑源性神经营养因子(BDNF)蛋白的表达水平,RT-PCR检测PSD95、Glu R1、Glu R2、CREB和BDNF m RNA的表达水平,免疫组化检测CPEB3蛋白的表达。[结果]Morris水迷宫结果显示:中高剂量染铝组大鼠的学习记忆能力明显受损。中、高剂量染铝组大鼠第3、4、5天的逃避潜伏期均高于同时间点对照组大鼠(分别延长了4.88、7.24、3.92 s和6.41、9.27、6.08 s,P<0.05),第6天目标象限停留时间和穿越平台次数均低于对照组(分别减少了13.21、16.46 s和0.9、1.6次,P<0.05)。Western blotting结果显示,中、高剂量染铝组大鼠海马组织中CPEB3(0.50±0.06、0.33±0.07)、PSD95(0.45±0.08、0.28±0.06)、GluR1(0.38±0.07、0.31±0.06)、GluR2(0.45±0.08、0.33±0.09)、CREB(0.58±0.11、0.41±0.07)和BDNF(0.49±0.03、0.33±0.05)蛋白表达水平均低于对照组(1.00±0.00)(P<0.05)。RT-PCR结果显示,中、高剂量染铝组大鼠海马中PSD95、GluR1、GluR2、CREB、BDNF的mRNA表达水平均低于对照组,P<0.05。免疫组化结果显示,CPEB3蛋白主要表达于大鼠的海马组织的神经元胞质中,且随着染铝浓度的增加而降低。[结论]亚慢性�[Background]The neurotoxicity of aluminum is characterized by impaired learning and memory,and decreased synaptic plasticity is the main mechanism of the impairment,but associated molecular mechanism is not clear.[Objective]This experiment is designed to investigate the effects of subchronic aluminum exposure on the expression of cytoplasmic polyadenylation element binding protein 3(CPEB3)and synaptic plasticity in rat hippocampus.[Methods]Forty two-month-old healthy male SD rats were randomly divided into four groups:control group,low-dose aluminum group(10μmol·kg^(-1)),middle-dose aluminum group(20μmol·kg^(-1)),and high-dose aluminum group(40μmol·kg^(-1)),with 10 rats in each group.The rats of the aluminumexposed groups were intraperitoneally injected of 0.1 m L per 100 g body weight maltol aluminum every other day for three months.The rats of the control group were given 0.9%sodium chloride solution.Morris water maze was used to test the learning and memory ability of the rats.The protein expressions of CPEB3,postsynaptic dense protein 95(PSD95),ionic glutamate receptor 1(Glu R1),ionic glutamate receptor 2(Glu R2),c AMP-response element binding protein(CREB),and brain-derived neurotrophic factor(BDNF)were detected by Western blotting.The m RNA expressions of PSD95,Glu R1,Glu R2,CREB,and BDNF were tested by RT-PCR.The expression of CPEB3 was also determined by immunohistochemistry.[Results]The results of Morris water maze showed that the learning and memory ability of the rats exposed to medium and high doses of aluminum were significantly impaired.The escape latencies on the 3 rd,4 th,and 5 th days in the middle-and high-dose aluminum groups were longer than those in the control group at the same time point(increased by 4.88,7.24,and 3.92 s for the middle-dose group,and 6.41,9.27,and 6.08 s for the high-dose group,respectively,P<0.05),the time of staying in target quadrant was shorter(shortened by 13.21 and 16.46 s respectively,P<0.05),and the times of crossing platform were decreased(reduced by 0.9 and

关 键 词：多聚腺苷酸化元件结合蛋白3 铝 突触可塑性 学习记忆能力 

分 类 号：R135[医药卫生—劳动卫生]