目的 探討大黃酚對(duì)小鼠腦c-fos和c-jun mRNA表達(dá)的影響及與學(xué)習(xí)記憶的關(guān)系。方法 昆明種小鼠,隨機(jī)分4組:對(duì)照組和大黃酚低、中、高(0.1、1.0、10.0 mg/kg)劑量組(每組n=20),避暗實(shí)驗(yàn)和Morris水迷宮實(shí)驗(yàn)觀察小鼠空間學(xué)習(xí)記憶的變化;RT-PCR檢測(cè)c-fos和c-jun mRNA表達(dá)。原代培養(yǎng)小鼠皮層星形膠質(zhì)細(xì)胞,不同劑量大黃酚(0.1、1.0、10 μg/mL)處理細(xì)胞1、2、3周;大黃酚(1.0、10 μg/mL)和谷氨酸(50 μmol/L)加或不加非競(jìng)爭(zhēng)性N-甲基-D-天冬氨酸(NMDA)受體抑制劑MK-801(1 μmol/L),RT-PCR檢測(cè)c-fos和c-jun mRNA表達(dá)。結(jié)果 中、高劑量大黃酚可提高小鼠空間學(xué)習(xí)記憶能力,同時(shí)上調(diào)c-fos和c-jun mRNA表達(dá);MK-801完全抑制大黃酚及谷氨酸誘導(dǎo)星形膠質(zhì)細(xì)胞c-fos和c-jun mRNA表達(dá)上調(diào)作用。結(jié)論 大黃酚可能通過(guò)激活谷氨酸受體上調(diào)c-fos和c-jun基因表達(dá),并提高小鼠空間學(xué)習(xí)記憶能力。

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.

河北省自然基金資助項(xiàng)目(H2012405016);河北省教育廳優(yōu)秀青年基金資助項(xiàng)目(Y2012002);河北北方學(xué)院創(chuàng)新人才項(xiàng)目(CXRC1325);河北北方學(xué)院校級(jí)重大項(xiàng)目(ZD201310)