环磷酸腺苷效应元件结合蛋白/脑源性神经营养因子信号通路在调心方改善APP/PS1小鼠学习记忆中的作用

Role of cAMP Response Element Binding Protein/Brain-derived Neurotrophic Factor Signaling Pathway in Tiaoxin Formula Improving Learning and Memory of APP/PS1 Mice

目的通过观察APP/PS1双转基因阿尔茨海默病(AD)小鼠海马环磷酸腺苷效应元件结合蛋白(CREB)/脑源性神经营养因子(BDNF)信号通路的变化,探讨调心方对APP/PS1双转基因AD小鼠学习记忆的影响机制。方法将3月龄APP/PS1雄性小鼠54只随机分为模型组(n=18)、多奈哌齐组(n=18)和调心方组(n=18);另设同月龄同品系的C57/BL6雄性小鼠18只为对照组。各给药组给予相应药物。给药12周后,每组采用Morris水迷宫进行行为学测试,采用实时荧光定量聚合酶链反应(RT-q PCR)法检测海马CREB mRNA和BDNF mRNA表达的变化,Western blotting法检测海马磷酸化CREB(p-CREB)、BDNF蛋白表达的变化。结果与模型组比较,调心方组逃避潜伏期显著缩短(P<0.001),在原平台所在象限停留的时间百分比增加(P<0.05),海马CREB mRNA、BDNF mRNA表达较模型组均增加(P<0.05),海马p-CREB、BDNF蛋白表达较模型组明显增加(P<0.01)。结论调心方可有效改善APP/PS1双转基因AD小鼠的空间学习记忆,可能与上调CREB/BDNF信号通路有关。

Objective To observe the changes of c AMP response element binding protein(CREB)/brain-derived neurotrophic factor(BDNF) signaling pathway in the hippocampus of APP/PS1 double transgenic Alzheimer's disease mice, and investigate the effects of Tiaoxin formula on learning and memory.Methods Totally, 54 three-month-old APP/PS1 transgenic mice were randomly divided into model group(n=18), positive control(donepezil) group(n=18) and Tiaoxin formula group(n=18). Another 18 three-month-old C57/BL6 wild mice were chosen as normal group with same strain and same age. All administration groups received relevant medicine. Twelve weeks later, Morris water maze test was used to test the behavior. The real-time quantitative polymerase chain reaction(RT-qPCR) was used to detect the expression of CREB mRNA and BDNF mRNA in hippocampus. Western blotting was used to detect the expression of phosphorylated CREB(p-CREB) andBDNF in hippocampus.Results Compared with the model group, the escape latency significantly shortened(P<0.01), the percentage of staying time in the quadrant of original platform significantly increased(P<0.05), the expression of CREB mRNA and BDNF mRNA in hippocampus significantly increased(P<0.05), and the expression of p-CREB and BDNF protein in hippocampus significantly increased(P<0.01) in Tiaoxin formula group.Conclusion Tiaoxin formula could improve the spatial learning and memory of APP/PS1 double transgenic mice with AD, which might be related to the up-regulation of CREB/BDNF signaling pathway.