APP5肽类似物P165对链脲佐菌素双侧侧脑室注射大鼠海马神经元突触的保护作用

目的观察APP5肽类似物P165对双侧侧脑室注射链脲佐菌素(STZ)大鼠海马神经元突触相关蛋白表达的影响。方法雄性Wistar大鼠45只,随机分为对照组、模型组和治疗组。模型组、治疗组大鼠脑室注射STZ制作痴呆模型,3周后,治疗组以APP5肽类似物P165灌胃治疗,用药4周后,采用Morris水迷宫进行行为学测试;免疫组织化学染色及Western blotting方法观察突触素、α-突触核蛋白和突触后致密区-95蛋白(PSD-95)的表达;电镜观察海马CA1区超微结构改变。结果模型组游泳时间显著长于对照组和治疗组。免疫组织化学染色及Westernblotting均显示模型组海马内突触素、PSD-95蛋白表达与对照组和治疗组相比显著减少,而α-突触核蛋白显著增多。电镜观察可见模型组海马CA1区神经元出现退行性改变,神经毡内突触结构异常。结论脑室注射STZ可影响大鼠海马突触相关蛋白的表达,引起海马神经元和突触的超微结构病变,导致大鼠学习记忆能力减退。APP5肽类似物P165可影响突触蛋白的表达,改善突触功能,有助于恢复大鼠的学习、记忆能力。

THE PROTECTIVE EFFECT OF ANALOG 165 OF APP5-MER PEPTIDE ON SYNAPSES OF NEURON IN HIPPOCAMPUS OF STZ-AD RATS

Objective To investigate the effects of analog 165 of APP5-mer peptide on the expression of synaptic related proteins in neurons of the hippocampus through intracerebroventricular(ICV) injection of streptozotocin(STZ) in rats. Methods A total of 45 Wistar rats were randomly divided into control group, model group and treated group. Rats in the model and treated groups received intracerebroventricular injection of STZ bilaterally. After three weeks, rats in the treated group received gastric perfusion of analog 165 of APP5-mer peptide. After the four week treatment, the memory of the rats was surveyed by Morris water maze test.The expressions of synaptic related proteins, such as postsynaptic density_95 protein(PSD-95), synaptophysin and α-Synuclein, were tested with immunohistochemical staining and Western blotting. The ultra structure of the neurons of hippocampus was observed with transmission electron microscope. Results 1.Full course swimming time was obviously longer in the model group than that those in the treated and control groups. 2.In the model group, the expressions of PSD-95 and synaptophysin decreased,and the expression of α-Synuclein increased. The treated group normalized the expression of the targeted proteins. 3.Retrograde degeneration of the neurons of hippocampus was observed in the model group, and dysmorphic synapses were observed in the neuropil. Conclusion There are low PSD-95, synaptophysin levels and high α-Synuclein levels in the ICV injected brain of STZ rats. Analog 165 of APP5-mer peptide improves the expression of the three proteins to some extent; therefo