亚慢性铝暴露抑制大鼠海马区突触可塑性PI3K/AKT/mTOR信号通路机制  

Sub-chronic aluminum exposure inhibits synaptic plasticity in hippocampus of rats via inhibiting PI3K/AKT/mTOR signaling pathway

作　　者：薛星莉 李欢[1] 李亚芹 李亮 潘宝龙[1] 郝艳霞 牛侨[1] XUE Xingli;LI Huan;LI Yaqin;LI Liang;PAN Baolong;HAO Yanxia;NIU Qiao(School of Public Health,Shanxi Medical University,Taiyuan,Shanxi 030001,China)

机构地区：[1]山西医科大学公共卫生学院,山西太原030001

出　　处：《中国职业医学》2020年第2期141-146,共6页China Occupational Medicine

基　　金：国家自然科学基金面上项目(81872599)。

摘　　要：目的研究亚慢性铝暴露对大鼠海马区突触可塑性的影响,探讨磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)/雷帕霉素靶蛋白(mTOR)信号通路在其中的作用机制。方法无特定病原体级成年健康雄性SD大鼠,按照体质量随机分为对照组和低、中、高剂量组,每组10只;分别予浓度为0、10、20、40μmol/kg体质量麦芽酚铝溶液腹腔注射,每周暴露5 d,持续3个月。染毒结束后,称量大鼠体质量,以Morris水迷宫实验检测大鼠学习记忆能力,以双电极绑定技术检测在体大鼠海马CA1区长时程增强(LTP)幅值,以免疫印迹法检测大鼠海马组织中PI3K、AKT和mTOR蛋白表达。结果暴露结束后,中、高剂量组大鼠体质量均低于对照组(P<0.05)。定位航行实验结果显示,实验第2~5天,中、高剂量组大鼠逃避潜伏期均低于同时间点对照组(P<0.05)。空间探索实验结果显示,4组大鼠目标象限停留时间和穿越平台次数分别比较,差异均无统计学意义(P>0.05)。高频刺激后1、30、60 min,3个剂量组大鼠海马CA1区LTP幅值均低于同时间点对照组(P<0.05),且大鼠海马CA1区LTP幅值均随着麦芽酚铝暴露剂量的增加而下降(P<0.01)。3个剂量组大鼠海马组织中PI3K、AKT和mTOR的蛋白相对表达水平均低于对照组(P<0.05),且上述3种蛋白相对表达水平均随着麦芽酚铝暴露剂量的增加而下降(P<0.01)。结论亚慢性铝暴露可导致大鼠海马区突触可塑性出现剂量依赖性抑制,进而损害大鼠空间学习能力;该过程可能与铝抑制PI3K/AKT/mTOR信号通路有关。Objective To study the effect of sub-chronic aluminum exposure on synaptic plasticity in the hippocampus of rats and to explore the mechanism of phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)/rapamycin target protein(mTOR)signaling pathway.Methods Specific pathogen free adult healthy male SD rats were randomly divided into control group and low-,medium-and high-dose groups based on body weight,with 10 rats in each group.Rats were treated with maltol aluminum solution at the concentrations of 0,10,20 and 40μmol/kg body weight by intraperitoneal injection,5 days per week for 3 months.After the exposure,rats were weighed.Morris water maze was used to test the learning and memory ability,and the two-electrode binding technique was used to record the long-term potentiation(LTP)amplitude in the hippocampus CA1 area of rats.The protein expression of PI3K,AKT and mTOR in rat hippocampus tissues was detected by Western blot.Results After the exposure,the body weights of rats in the medium-and high-dose groups were lower than that of the control group(P<0.05).The results of the positioning navigation experiment showed that the escape latencies of the rats in the medium-and high-dose groups were shorter than that in the control group during the 2nd to 4th days of the experiment(P<0.05).The results of space exploration experiments showed that there was no statistical difference on the target quadrant retention time and the number of crossing the platform among the 4 groups(P>0.05).At 1,30,and 60 min after high-frequency stimulation,the LTP amplitudes in the hippocampus CA1 area of the aluminum-treated groups were lower than that of the control group at the same time point(P<0.05),and the LTP amplitudes of hippocampus CA1 area of rats decreased with the increase of maltol aluminum exposure dose(P<0.01).The relative expression of PI3K,AKT and mTOR protein in the hippocampus tissues of the aluminum-treated groups was lower than that of the control group(P<0.05),and the relative expression of the above three proteins

关 键 词：铝 学习记忆 突触可塑性 长时程增强 磷脂酰肌醇3激酶 蛋白激酶B 雷帕霉素靶蛋白 大鼠 

分 类 号：R135.1[医药卫生—劳动卫生] R114[医药卫生—公共卫生与预防医学]