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、10 μg/mL)处理细胞1、2、3周;大黄酚(1.0、10 μg/mL)和谷氨酸(50 μmol/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(1 μmol/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 study the effects of chrysophanol (Chry) on the mRNA expression of c-fos and c-jun in brain of mice and the relationship with learning and memory. Methods Eighty mice were randomly divided into control group and Chry group (n=20, 0.1, 1.0, and 10.0 mg/kg). Passive avoidance test and Morris water maze test were used to examine the abilities of learning and memory in mice. RT-PCR was used to detect mRNA expression of c-fos and c-jun. Primary cultured mouse astrocytes were treated by different concentration of Chry (0.1, 1.0, 10.0 μg/mL) for 1, 2, 3 weeks, or cells were treated by Chry (1.0 and 10.0 μg/mL) and glutamate (50 μmol/L) and non-NMDA antagonists MK801(1 μmol/L) for 2 weeks. Results Chry (1.0 and 10.0 mg/kg) can significantly improve the learning and memory of mice. And Chry (1.0 and 10.0 mg/kg) in vivo or (1.0 and 10.0 μg/mL) in vitro can upregulate the mRNA expression of c-fos and c-jun. However, low concentration of Chry had no effect. MK-801 completely inhibited Chry and glutamate-induced mRNA upregulation of c-fos and c-jun. Conclusion Chry may increase gene expression of c-fos and c-jun by activating glutamate receptor and improve spatial learning and memory in mice.

河北省自然基金资助项目(H2012405016);河北省教育厅优秀青年基金资助项目(Y2012002);河北北方学院创新人才项目(CXRC1325);河北北方学院校级重大项目(ZD201310)