目的:探讨cAMP反应元件结合蛋白(CREB)在姜黄素改善gp120所致大鼠学习记忆障碍中的作用。方法:SD大鼠随机分为6组:对照组、假手术组、模型组、姜黄素低、中和高剂量治疗组;除对照组、假手术组外其余4组侧脑室缓慢注射5μL的gp120,连续3d。第4天开始,低、中、高剂量治疗组分别每天给予50、100、200mg/kg的姜黄素灌胃,对照组、假手术组和模型组大鼠用双蒸水灌胃,连续灌胃14d。各组大鼠进行水迷宫测试,并分组进行海马磷酸化的CREB(pCREB)免疫组化染色。结果:①Morris水迷宫空间探索实验显示模型组大鼠反应迟钝,寻找目标象限所需的时间较长,在目标象限停留的时间及穿越次数明显短于对照组(P〈0.05);姜黄素低、中、高剂量治疗组大鼠寻找目标象限所需时间缩短,在目标象限停留的时间及穿越次数明显长于模型组(P〈0.05),其中姜黄素低剂量组效果更好(P〈0.05)。②免疫组化结果显示模型组大鼠海马内pCREB的表达与对照组相比有所降低(P〈0.01),姜黄素各剂量治疗组pCREB的表达有所上调。结论:姜黄素具有改善gp120所致大鼠学习记忆障碍的作用,其机制可能与增加海马CREB的磷酸化水平有关。
Aim:To investigate the role of CREB in curcumin improve learning and memory dysfunction in rats induced by gpl20. Methods: The SD rats were divided into six groups: control group, sham group, model group, low dose curcumin group, middle dose curcumin group and high dose curcumin group. Except control and sham group, the others four groups received slowly 5 μL/d gpl20 which dissolved in artificial cerebrospinal fluid (ACSF) for 3 days. From the fourth day, the rats of low, middle, high dose curcumin groups were treated with 50,100,200 mg/kg curcumin every day, respectively. The others groups were treated with redistilled water. The treatment will last for 14 days. Subsequently, the water maze test and pCREB immunohistochemical staining in hippocampus were applied to evaluate the effect of curcumin on the rats. Results: (1) Space probe test showed that the rats in model group had a bit clumsy and spent a significantly longer time to seek the target quadrant, and that the rats in model group had the shorter retention time and less frequency of accrossing target quadrant compared with those in control group (P 〈0. 05). However, the rats in low, middle, high dose curcumin groups spent a significantly shorter time to seek the target quadrant and had the longer retention time and more frequency of accrossing target quadrant compared with those in model group ( P 〈 0.05 ), and low dose curcumin group was better than the other two groups ( P 〈 0. 05). (2) Immunohistochemical staining showed that the expressions of pCREB in model group decreased compared with the control groups ( P 〈 0. 01 ), while the expressions of pCREB in low,middle and high dose curcumin groups increased compared with the model groups. Conclusion:The mechanism of curcumin improving learning and memory dysfunction induced by gp120 maybe related with upregulated the expression of phosphorylated CREB.