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目的:探讨亚慢性铝暴露对大鼠学习记忆能力的影响,分析大脑皮质即刻早基因表达变化,初步探索铝对认知功能损害的毒性作用及机制。方法:随机将孕大鼠分为对照组和低、中、高染铝组,染毒组仔鼠出生后首日连续染毒3个月,然后各组大鼠进行水迷宫测试,铝含量检测,皮质神经细胞病理学观察,皮质c-fos mRNA和蛋白表达水平检测。结果:铝含量随染毒剂量增加而升高;染铝组学习记忆能力明显低于对照组,并呈剂量-效应关系;染铝组皮质神经细胞呈现神经纤维稀疏、神经元细胞脱失甚至空泡样变性等病理改变;中、高剂量组皮质区c-fos mRNA表达水平分别低于对照组和低剂量组。染铝组皮质区c-Fos蛋白表达水平低于对照组。随染毒剂量增加,c-fos mRNA和蛋白表达水平降低并具有一定的相关性。结论:亚慢性铝暴露损害大鼠学习记忆能力,其机制可能与铝造成皮质神经细胞功能减弱(即刻早基因c-fos mRNA和蛋白表达水平下降)有关。
Aims: To investigate the effect of subchronic aluminum exposure on learning and memory in rats, analyze the expression of immediate early genes in the cerebral cortex, and to explore the toxic effects and mechanism of aluminum on cognitive impairment. Methods: Pregnant rats were randomly divided into control group and low, medium and high aluminum groups. The exposed groups were exposed to the first day after birth for 3 consecutive months. The rats in each group were subjected to water maze test and aluminum content test , Cortical neuronal pathology, cortical c-fos mRNA and protein expression levels were detected. Results: The content of aluminum increased with the increase of dose. The ability of learning and memory of the aluminum-treated group was significantly lower than that of the control group, and showed a dose-effect relationship. The cortical neurons in the aluminum-exposed group showed sparse nerve fibers, neurons lost even Vacuolar degeneration and other pathological changes; c-fos mRNA expression in the cortex of middle and high dose group were lower than the control group and low dose group. The expression of c-Fos protein in the cortex of aluminum-exposed group was lower than that of the control group. With the increase of the dose, the expression of c-fos mRNA and protein decreased and had a certain correlation. CONCLUSION: Subchronic aluminum exposure impairs the ability of learning and memory in rats. The mechanism may be related to the decreased function of cortical neurons caused by aluminum (immediate reduction of c-fos mRNA and protein expression).