【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。更多还原

【Abstract】 Objective To study the changes of Extracellular Signal Regulated Kinase（ERK）content and its mRNA expression level that caused by chronicaluminium 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 gavage 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.更多还原