中文摘要：

目的探讨慢性复合应激对大鼠学习与记忆的作用,以及Ca^2＋/钙调蛋白依赖性蛋白激酶Ⅱ（CaMKⅡ）、钙调蛋白（CaM）mRNA、环腺苷酸反应元件结合蛋白（CREB）mRNA水平的变化及其在学习和记忆中的作用。方法Wistar大鼠被随机分为慢性复合应激组（16只）和对照组（16只）。慢性复合应激组动物给予6周的慢性复合应激刺激,制备慢性复合应激模型;Morris水迷宫和Y迷宫测试大鼠空间学习和记忆的行为表现;免疫组织化学、Western blotting和RT-PCR检测大鼠海马CaMKⅡ、CaM mRNA和CREB mRNA水平的变化;观察分析CaMKⅡ在海马CA1和CA3区的分布和表达;电镜观察海马CA3区突触间隙的宽度和突触后致密物质（PSD）的厚度的变化。结果慢性复合应激6周后,应激组大鼠的学习与记忆能力均高于对照组（P〈0.05,P〈0.01）;应激组海马CA3区突触间隙的宽度为5.0580±1.4216,PSD的厚度为20.9547±2.5693。与对照组相比,海马CA1和CA3区辐射层和始层CaMKⅡ的免疫染色明显增强,特别是始层;CaMKⅡ、CaM mRNA及CREB mRNA水平均明显增高（P〈0.05,P〈0.01）。结论慢性复合性应激后,大鼠的学习与记忆能力增强;海马CaMKⅡ、CaM mRNA和CREB mRNA水平增加可能是参与了慢性复合应激性学习记忆增强的机制。

英文摘要：

Objective To investigate the effects of chronic multiple-stress on learning and memory and on the levels of calcium/calmodulin-dependent protein kinase Ⅱ （CaMK Ⅱ ）, calmodulin （CAM） mRNA, and cAMP-response element binding protein （CREB） mRNA in the hippocampus of rats and possible mechanisms. Methods The Wistar rats were divided randomly into stressed （ n = 16） and control groups （ n = 16）. The stressed group was given chronic multiple-stress for 6 weeks to prepare the chronic multiple-stressed model. The rats＇ performance of spatial learning and memory was tested by Morris water maze （MWM） and Y-maze. The expressions of CaMK Ⅱ , CaM mRNA and CREB mRNA in hippocampus of rats＇ were detected by immunohistochemistry, Western blotting and RT-PCR respectively. The width of synaptic cleft and the thickness of post-synaptic densities （PSD） were observed in the hippocampal CA3 region of rats under electron microscopy. Results After the exposure to chronic multiple-stress for 6 weeks, the ability of learning and memory of the stressed group was higher than that of the control group （ P 〈 0.05, P 〈 0.01 ）. The width of synaptic cleft was 5. 0580 ± 1.4216 and the thickness of PSD was 20. 9547 ± 2. 5693 in the hippocampal CA3 of stressed rats. Compared with the control group, the CaMK Ⅱ immunostaining of stressed animals was stronger in the stratum radiatum and oriens of hippocampal CA1 and CA3, especially in the stratum oriens. The expressions of CaMK H , CaM mRNA, and CREB mRNA in the hippocampus of the stressed group was significantly higher （P 〈 0.05, P 〈 0.01）. Conclusion The capacity of learning and memory was enhanced following chronic multiple-stress. The increase in the levels of hippocampal CaMK H , CaM mRNA, and CREB mRNA revealed that they might have participated in the enhancing effect of chronic multiple-stress on learning and memory.