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为探讨长时间应用一氧化氮(NO)对学习记忆功能和神经系统可塑性的影响,以及NO与c-fos基因表达的关系,分别给初断乳的大鼠灌胃NO前体左旋-精氨酸(L-Arg)或一氧化氮合酶抑制剂L-NAME,用Morris水迷宫检测大鼠的学习记忆功能,用免疫组化技术和HE染色检测大脑皮质和海马CA1、CA3、DG区的神经元型一氧化氮合酶(nNOS)和c-fos基因的表达以及神经细胞数目的变化。将大鼠随机分成L-Arg组、L-NAME组和对照组。大鼠断乳后分别每天用L-Arg[200mg/(kg.d)]、L-NAME[50mg/(kg.d)]和等剂量的蒸馏水灌胃,持续3个月。结果显示:长期应用NO前体L-Arg可明显缩短大鼠的寻台潜伏期,促进nNOS和c-fos基因的表达,同时大脑皮质和海马CA1、CA3、DG区的神经元数目增加;而长期应用一氧化氮合酶抑制剂L-NAME可抑制大鼠寻台潜伏期的缩短和nNOS、c-fos基因的表达,同时大脑皮质和海马CA1、CA3、DG区的神经元数目减少。因此我们认为长时间应用NO可促进神经系统c-fos基因的表达和幼鼠神经系统的发育,即可塑性的变化,继而影响大鼠的学习记忆功能。
To investigate the effect of long-term application of nitric oxide (NO) on learning and memory function and nervous system plasticity, and the relationship between NO and c-fos gene expression, (L-Arg) or L-NAME, a nitric oxide synthase inhibitor, was used to detect the learning and memory function of rats by Morris water maze. Immunohistochemistry and HE staining were used to detect the expressions of CA1, CA3 and DG in the cerebral cortex and hippocampus Changes in the expression of neuronal nitric oxide synthase (nNOS) and c-fos genes and the number of nerve cells. The rats were randomly divided into L-Arg group, L-NAME group and control group. Rats were orally administered with L-Arg [200 mg / (kg · d)], L-NAME [50 mg / (kg · d)] and distilled water of equal dose daily for 3 months after weaning. The results showed that long-term application of NO-L-Arg significantly shortened the search latency and promoted the expression of nNOS and c-fos in rats, meanwhile, the number of neurons in CA1, CA3 and DG of cerebral cortex and hippocampus increased. L-NAME, a nitric oxide synthase inhibitor, can inhibit the shortening of search latency and the expression of nNOS and c-fos genes in rats, and reduce the number of neurons in CA1, CA3 and DG of cerebral cortex and hippocampus. Therefore, we think that prolonged application of NO can promote the expression of c-fos gene in nervous system and the development of the nervous system of young rats, that is, the change of plasticity, and then affect the learning and memory function of rats.