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目的探讨大黄酚对小鼠脑c-fos和c-jun mRNA表达的影响及与学习记忆的关系。方法昆明种小鼠,随机分4组:对照组和大黄酚低、中、高(0.1、1.0、10.0 mg/kg)剂量组(每组n=20),避暗实验和Morris水迷宫实验观察小鼠空间学习记忆的变化;RT-PCR检测c-fos和c-jun mRNA表达。原代培养小鼠皮层星形胶质细胞,不同剂量大黄酚(0.1、1.0、10μg/m L)处理细胞1、2、3周;大黄酚(1.0、10μg/m L)和谷氨酸(50μmol/L)加或不加非竞争性N-甲基-D-天冬氨酸(NMDA)受体抑制剂MK-801(1μmol/L),RT-PCR检测c-fos和c-jun mRNA表达。结果中、高剂量大黄酚可提高小鼠空间学习记忆能力,同时上调c-fos和c-jun mRNA表达;MK-801完全抑制大黄酚及谷氨酸诱导星形胶质细胞c-fos和c-jun mRNA表达上调作用。结论大黄酚可能通过激活谷氨酸受体上调c-fos和c-jun基因表达,并提高小鼠空间学习记忆能力。
Objective To investigate the effect of chrysophanol on the expression of c-fos and c-jun mRNA in brain and its relationship with learning and memory in mice. Methods Kunming mice were randomly divided into 4 groups: the control group and the low, middle and high doses of 0.1, 1.0 and 10.0 mg / kg of chrysophanol (n = 20 each group), the dark-avoidance experiment and Morris water maze test The changes of spatial learning and memory in mice were observed. The mRNA expressions of c-fos and c-jun were detected by RT-PCR. Primary cultured mouse cortical astrocytes were treated with different doses of chrysophanol (0.1,1.0,10μg / mL) for 1, 2 and 3 weeks. Chrysophanol (1.0, 10μg / mL) and glutamic acid 50μmol / L) with or without noncompetitive N-methyl-D-aspartate (NMDA) receptor MK-801 (1μmol / L) expression. Results, high-dose chrysophanol can improve spatial learning and memory in mice, while up-regulating c-fos and c-jun mRNA expression; MK-801 completely inhibited chrysophanol and glutamate-induced astrocyte c-fos and c -jun mRNA expression up-regulation. Conclusion Chrysophanol may up-regulate the expression of c-fos and c-jun genes by activating glutamate receptors and improve spatial learning and memory in mice.