链脲佐菌素对APP／PS1转基因小鼠学习记忆及JNK信号通路的影响

Effect of streptozotocin on learning memory and JNK signaling pathway in APP/PS1 transgenic mice

目的 观察链脲佐菌素（streptozotocin,STZ）对APP/PS1转基因小鼠学习记忆和海马组织MKK4、JNK、c-Jun磷酸化水平的影响.方法 3月龄APP/PS1转基因小鼠腹腔内注射STZ,采用Morris水迷宫实验观测学习记忆功能,应用尼氏染色观察海马神经元细胞形态,应用免疫印迹法检测海马组织内MKK4、JNK和c-Jun的表达水平.结果 水迷宫隐蔽平台实验中,从第2天到第5天,给予STZ后APP/PS1转基因小鼠逃避潜伏期和目标路径均明显长于对照组（P＜0.05或P＜0.01）；Nissl染色显示STZ组小鼠海马神经元损伤明显；与对照组比,STZ组海马组织中磷酸化JNK和c-Jun的表达水平明显增高,分别增高到217.78 ±23.49和189.27±17.80（P＜0.01）.结论 STZ可使APP/PS1转基因小鼠学习记忆功能减退,神经元损伤,其机制可能与JNK信号转导通路有着密切的关系.

Objective To investigate the effect of streptozotocin （STZ） on learning,memory and expression of p-MKK4,p-JNK and p-Jun in APP transgenic mice.Methods Three-month-old APP/PS1 mice were intraperitoneally injected with STZ.Learning and memory function was performed by Morris water maze.The changes of neuronal morphology in hippocampum were observed by Nissl staining.The expression of MKK4,JNK and c-Jun were detected in hippocampal tissues by Western blotting.Results In the hidden platform experiment of Morris maze,the escape latencies and the pathway length of STZ-induced diabetic mice were longer than those in controls from the 2nd to 5th day（P 〈 0.05 or P 〈 0.01）.The Nissl staining showed that some neurons in hippocampum of STZ-treated mice were displayed changes of injury.Compared with the vehicle control,the expression levels of pJNK and p-c-Jun were increased by 217.78 ± 23.49 and 189.27 ± 17.80,respectively （P 〈 0.01）.Conclusion STZ can decrease the learning and memory function and injury the neurons,which maybe relate to the JNK signal pathway.