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作 者:王彪[1] 邢伟[1] 许金华[1] 时利德[1] 张玉霞[1]
机构地区:[1]中国医科大学生物化学与分子生物学教研室,沈阳110001
出 处:《中国公共卫生》2006年第12期1464-1466,共3页Chinese Journal of Public Health
基 金:国家自然科学基金(30371229)
摘 要:目的研究慢性铝中毒对大鼠海马细胞外信号调节蛋白激酶(ERK)蛋白及mRNA表达水平的变化,探讨铝中毒对学习记忆机制的影响。方法选择断乳后Wistar大鼠,用不同浓度AlCl3的水饲养3个月。测量大鼠海马长时程增强(LTP),用改良的Takai法测定丝裂原活化蛋白激酶(MAPK)活性的变化,蛋白印迹(Western blotting)方法检测ERK1/2的蛋白含量,RT-PCR方法检测ERK2的mRNA表达。结果(1)各染铝组MAPK活性降低且与对照组比较差异有统计学意义(P<0.05);(2)ERK1/2蛋白表达的比较:①ERK2在大鼠海马中的蛋白含量高于ERK1;②染铝组ERK1/2非磷酸水平与对照组比较均有所下降(P<0.05),但染铝组之间差异无统计学意义(P>0.05);③染铝组ERK1/2磷酸化水平与对照组的比较均有下降(P<0.05),染铝组之间的差异有统计学意义(P<0.05)。(3)染铝组ERK2的mRNA表达与对照组比较明显降低,但染铝组之间差异无统计学意义(P>0.05)。结论慢性铝中毒不仅影响大鼠海马中ERK2的mRNA表达水平,同时也影响ERK1/2的蛋白表达水平的降低,造成有丝分裂原活化蛋白激酶(MAPK)活性的下降,损害LTP的形成,从而影响学习记忆功能下降。Objective To study the changes of Extracellular Signal Regulated Kinase(ERK) content and its mRNA expression level that caused by chronic - aluminium exposure, which can alter the amplitude value of long - term potentiation (LTP), to go deep into the mechanism of learning and memory. Methods The ablactated Wistar rats were used to establish the chronic - aluminium exposed models by the garage of AlCl3 of different concentrations in the drinking water and LTP in hippocampus of rats was measured. The mitogen- activiated protein kinase (MAPK)activity was determined by modified Takai Method. ERK1/2 content of hippocampus and the mRNA expression level of ERK2were determined by Western Blot and RT - PCR methods individually, Results ( 1)The MAPK activity of AlCl3 exposed groups was obviously lower than that of control groups( P 〈 0.05). (2)The content of ERK1/2 in the hippocampus of AlCl3 - exposed groups fell down comparing with that of control groups but there was no statistic difference between the AlCl3 - exposed groups (P 〉 0.05 ). (3)The amount of ERK2 was higher than that of ERK1 in the nervous system and the expression of ERK2 protein of aluminium exposed groups showed a downwards tendency comparing with that of control groups( P 〈 0.05). (4)ERK1/2 phosphorylation level of aluminium exposed groups obviously decreased comparing with that of control group(P 〈 0.05). (5)The mRNA expression of ERK2 of AlCl3 - exposed groups fell down comparing with that of control groups but there was no statistic difference between the AlCl3 - exposed groups( P 〉 0.05 ), Conclusion Chronic aluminum exposure can affect not only the mRNA expression of ERK2 but also the expression of ERK1/2 protein and its phosphorylation level, in hence, can reduce the activity of MAPK, damaging the formation of LTP and consequently impairing the ability of learning and memory.
关 键 词:铝 长时程增强 细胞外信号调节蛋白激酶 学习与记忆 海马
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