利拉鲁肽对脲链佐菌素诱导阿尔茨海默病大鼠认知功能及Tau蛋白磷酸化的影响

目的：探讨利拉鲁肽对脲链佐菌素（STZ）诱导阿尔茨海默病（AD）大鼠认知功能及Tau蛋白磷酸化的影响。方法：Wistar雄性大鼠24只，随机分为空白对照组、假手术组、模型组和治疗组，每组6只，采用单次右侧脑室注射STZ（3 mg/kg）诱导AD大鼠，14 d后连续4周皮下注射利拉鲁肽干预；利用Morris水迷宫实验检测大鼠认知功能改变，利用免疫组织化学法和Western blot法检测Ser396位点磷酸化的Tau蛋白表达。结果：Morris水迷宫实验结果显示，与空白对照组相比，假手术组大鼠的逃逸潜伏期和穿越平台次数差异无统计学意义（P>0.05）；与假手术组相比，模型组大鼠逃逸潜伏期和穿越平台次数增加（P<0.05）；与模型组相比，利拉鲁肽治疗组大鼠逃逸潜伏期和穿越平台次数减少（P<0.05）。免疫组化和Western blot检测结果显示，模型组大鼠海马组织中Ser396位点磷酸化的Tau蛋白表达增加（P<0.05），经利拉鲁肽干预后表达减少（P<0.05）。结论：利拉鲁肽能改善STZ诱导的AD大鼠空间学习记忆能力的损伤，降低大鼠海马区Ser396位点磷酸化的Tau蛋白表达。

Effects of liraglutide on cognitive function and phosphor ylation of Tau protein in streptozotocin-induced Alzheimer in rats

OBJECTIVE: To investigate effects of liraglutide on cognitive function and phosphorylation of Tau protein in a streptozotocin (STZ)-induced Alzheimer's disease (AD) in rats. METHODS: 24 male Wistar rats were randomly divided into blank control,sham operation,model and treatment groups,with 6 rats per group. For an AD rat model,each rat received a single injection of STZ (3 mg/kg) into the right intracerebroventricular region. After 14 days,rats in the treated group received subcutaneous injections of liraglutide for 4 weeks. Cognitive functions were detected using the Morris water maze test. Expressions of phosphorylation of Tau protein Ser396 were detected using immunohistochemistry (IHC) and Western blot methods. RESULTS: Results from the Morris water maze test show that both the escape latency and the number of times of crossing the platform for rats from the sham operation group were not significantly different from the blank control group (P>0.05). From the same test,results from the model rats were markedly increased over the sham operation group (P<0.05), that from the treated group were markedly decreased compared to the model group (P<0.05). Results from the IHC and Western blot analyses show that phosphorylations of the Tau protein Ser396 were increased significantly in the model rats (P<0.05) but decreased after liraglutide treatments (P<0.05). CONCLUSION: Our data show that liraglutide improved the STZ-induced damage of spatial learning and memory abilities and reduced expression of phosphorylation of Tau protein Ser396 in the hippocampi of rats.