目的探讨慢性复合应激对大鼠学习与记忆的作用,以及Ca2+/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。 Objective To investigate the effects of chronic multiple stress on learning and memory in rats and the effects of Ca2 + / CaMKⅡ, CaM mRNA and CREB mRNA Changes in Levels and Their Role in Learning and Memory. Methods Wistar rats were randomly divided into chronic stress group (16 rats) and control group (16 rats). Chronic multiple stress rats were given six weeks of chronic combined stress stimulation to prepare chronic complex stress model; Morris water maze and Y maze test of spatial learning and memory behavior; immunohistochemistry, Western blotting and RT-PCR The changes of CaMKⅡ, CaM mRNA and CREB mRNA in hippocampus of rats were observed. The distribution and expression of CaMKⅡ in CA1 and CA3 areas of hippocampus were observed and observed. The width of synaptic cleft and the thickness of PSD in hippocampal CA3 area were observed by electron microscopy The change. Results After six weeks of chronic combined stress, the learning and memory abilities of rats in stress group were significantly higher than those in control group (P <0.05, P <0.01). The width of synaptic cleft in CA3 of hippocampus was 5.0580 ± 1.4216, The PSD has a thickness of 20.9547 ± 2.5693. Compared with the control group, the immunostaining of CaMKⅡ in the radiation layer and the stratum CA1 in the hippocampus was significantly increased, especially in the basal layer. The levels of CaMKⅡ, CaM mRNA and CREB mRNA were significantly increased (P <0.05, P <0.01). CONCLUSION: The chronic learning and memory ability of rats increased after chronic multiple stress. The increase of CaMKⅡ, CaM mRNA and CREB mRNA in hippocampus may be involved in the mechanism of chronic multiple stress learning and memory enhancement.