硝酸镧对小鼠学习记忆低剂量兴奋效应及其机制研究  

STUDY ON THE MECHANISM OF HORMESIS OF LANTHANUM NITRATE ON LEARNING AND MEMORY OF MICE

作　　者：蒋建军[1] 尚兰琴[1] 杨晓华[1] 骆颖慧[1] 赵燕[1] 董辛欣[1] 郝卫东[1] 

机构地区：[1]北京大学公共卫生学院毒理学系,北京100083

出　　处：《现代预防医学》2007年第22期4225-4227,4232,共4页Modern Preventive Medicine

基　　金：北京市自然科学基金(5062025)

摘　　要：[目的]观察硝酸镧对小鼠学习记忆的低剂量兴奋效应及其与cAMP反应元件结合蛋白(CREB)和Jun-氨基末端激酶(JNK)蛋白磷酸化水平的关系。[方法]以0.002、0.02、0.2、2、20 mg/kg硝酸镧染毒ICR小鼠4周,每天测定小鼠水迷宫的反应时间和错误次数;试验结束时,取小鼠大脑分离海马和皮质,采用western blot测定p-CREB和p-JNK的含量。[结果]小鼠水迷宫的反应时间在染毒第4周时随着剂量的升高,呈现逐渐缩短,然后又逐渐延长的趋势,0.2 mg/kg组的反应时间最短;而错误次数则出现相反的趋势,2 mg/kg组的错误次数最少。硝酸镧经口染毒小鼠4周,0.2 mg/kg剂量组小鼠海马的CREB(6.20±3.2)和JNK(4.11±2.92)磷酸化水平升高,与溶剂对照组相比,差异有显著性。硝酸镧染毒各剂量组小鼠的皮质CREB和JNK磷酸化与对照组相比差异无显著性。[结论]硝酸镧经口染毒引起小鼠海马CREB和JNK蛋白的磷酸化水平升高,这与小鼠的学习记忆能力的变化的趋势一致,提示低剂量硝酸镧可能通过引起学习相关蛋白磷酸化水平的升高而对小鼠的空间学习记忆产生促进作用。[Objective]To observe the hormesis of La（NO3）3 at different concentrations on learning and memory of mice and study its correlation with phosphorylation level of cAMP-responsive element binding protein（CREB）and Jun-amino terminal-kinase（JNK）protein of hippocampus and cortex.[Methods]ICR mice were randomly divided into seven groups,including blank control group,control group,0.002,0.02,0.2,2,20 mg/kg lanthanum nitrate groups.Blank control and control groups were administrated with distilled water by lavage.Except for the blank group,mice in the other groups were studied the everyday learning and memory ability with water maze.All the mice were sacrificed after four weeks.The levels of Phospho-CREB protein and Phospho-JNK protein of hippocampus and cortex were determined by Western blotting.[Results]The reaction time of water maze for mice shortened along with the increase of lanthanum nitrate quantity at the fourth week,then prolonged gradually,and the reaction time in 0.2 mg/kg lanthanum nitrate group was the shortest.While the situation of mistake reaction frequency was on the contrary,and the mistake reaction frequency was the lowest in 2 mg/kg lanthanum nitrate group.The levels of Phospho-CREB protein（6.20 ± 3.2）and Phospho-JNK protein（4.11 ± 2.92）of hippocampus were significantly higher in 0.2 mg/kg lanthanum nitrate group than those in control group.While the levels of Phospho-CREB protein（6.20 ± 3.2）and Phospho-JNK protein（4.11 ± 2.92）of cortex in lanthanum nitrate groups were not significantly different from those in control group.[Conclusions]These changes of p-CREB protein and p-JNK protein in hippocampus of mice consist with the changes of learning and memory ability of mice.It indicates that low dose of lanthanum nitrate might prompt the learning and memory ability of mice by enhancing the phosphorylation of CREB protein and JNK protein.

关 键 词：硝酸镧 学习记忆 低剂量兴奋效应 P-CREB P-JNK 

分 类 号：R96[医药卫生—药理学]