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目的研究镧对大鼠海马钙调蛋白依赖性蛋白激酶(CaMKIV)、环磷酸腺苷反应元件结合蛋白(CREB)磷酸化和脑源性神经营养因子(BDNF)基因表达的影响,探讨镧损害学习记忆能力的机制。方法随机将Wistar雌性成年大鼠分成对照组和低、中、高剂量染镧组,低、中、高剂量染镧组孕鼠在产仔后分别饮用0.25%、0.5%和1.0%LaCl3溶液。各染镧组仔鼠在断乳前经吸吮母乳染镧,断乳后自行饮用0.25%、0.5%和1.0%LaCl3溶液染镧1个月。然后对仔鼠进行水迷宫和跳台试验,并测定仔鼠海马镧含量、CaMKIV和CREB磷酸化以及BDNF mRNA表达水平。结果水迷宫和跳台测试时,各染镧组仔鼠的学习记忆能力明显低于对照组,呈一定的剂量-效应关系。染镧组仔鼠海马镧含量显著高于对照组,且随染毒剂量增加而增加。中、高剂量染镧组仔鼠海马CaMKIV、CREB磷酸化以及BDNF mRNA表达水平显著低于对照和低剂量染镧组。结论在该试验条件下,镧损害大鼠学习记忆能力的机制可能与海马CaMKIV、CREB磷酸化和BDNF基因表达水平下降有关。
Objective To investigate the effects of lanthanum on the expression of CaMKIV, CREB and BDNF in rat hippocampus and the effects of lanthanum on learning and studying of lanthanum damage Memories of the mechanism. Methods Wistar female adult rats were randomly divided into control group and low, middle and high doses of lanthanum group, low, medium and high doses of lanthanum group pregnant rats were fed with 0.25%, 0.5% and 1.0% LaCl3 solution. The lanthanum groups were exposed to lanthanum by sucking breastmilk before weaning, and lanthanum was dyed with 0.25%, 0.5% and 1.0% LaCl3 solution for 1 month after weaning. Then water maze and jumping test were performed on the offspring, and the content of lanthanum in the hippocampus, the phosphorylation of CaMKIV and CREB and the expression of BDNF mRNA in offspring were measured. Results In the water maze test and jumping test, the learning and memory abilities of the Lanthanum group were significantly lower than those of the control group, showing a dose-response relationship. The content of lanthanum in the hippocampus of the lanthanum-exposed group was significantly higher than that of the control group, and increased with the increase of the dose of lanthanum. The levels of CaMKIV, CREB phosphorylation and BDNF mRNA expression in hippocampus of medium and high dose lanthanum group were significantly lower than those of the control and low dose lanthanum group. Conclusions The mechanism of lanthanum in learning and memory impairment may be related to the decrease of CaMKIV, CREB phosphorylation and BDNF gene expression in hippocampus.