AE-624对STZ侧脑室注射模型小鼠认知行为的影响及其机制研究

发布时间：2018-08-27 14:13

【摘要】：目的:在细胞水平考察AE-624对LPS诱导的PC12细胞损伤的保护作用。在动物水平研究AE-624对链脲佐菌素(STZ)侧脑室注射诱导的AD模型小鼠认知行为的影响,并探讨相关机制。方法:(1)以200μg/m L的LPS诱导PC12细胞建立损伤模型,并以5,10,20,40,60,80,100μg/m L的AE-624拮抗其作用,采用四甲基偶氮唑盐(MTT)法检测各组细胞存活率。(2)将昆明小鼠或BALB/c鼠按体重随机分为正常组,模型组,阳性对照组(Donepezil组),AE-624低、中、高剂量组。除正常组小鼠注射PBS外,其余各组均侧脑室注射STZ(30μg/μL,5μL)制备AD模型。然后给予5,15,45mg/kg的AE-624溶液灌胃15天。给药完成后,利用自主活动、新物体识别、O迷宫、水迷宫等行为学实验测试小鼠的认知行为,通过LTP实验观察AE-624对突触可塑性的影响,通过测定血清和海马组织内SOD活力、MDA含量观察AE-624对氧化作用的影响,通过尼氏染色观察AE-624对小鼠神经元的影响。结果:(1)细胞实验表明,AE-624给药组细胞存活率显著高于模型组(P0.05或P0.005),说明其对LPS诱导的PC12细胞损伤有明显的保护作用。(2)与模型组相比,AE-624给药组小鼠的认知行为有明显提高:其自主活动性增加(P0.05),新物体识别优先指数升高(P0.05),在O迷宫中开臂区域的时间明显增加(P0.05或P0.01),在水迷宫测试期逃避潜伏期明显缩短(P0.01或P0.005)。LTP有明显提高:AE-624给药组PS波增幅显著高于模型组(P0.05)。与正常组相比,模型组小鼠血清和海马组织内SOD活力明显降低(P0.05),MDA含量明显升高(P0.001)。与模型组相比,AE-624组在给药后能明显提高小鼠血清和海马组织SOD活力(P0.05或P0.001),降低血清和海马组织MDA含量(P0.05或P0.001)。尼氏染色发现,与正常组相比,模型组小鼠神经元数目明显减少(P0.01),与模型组相比,AE-624可以明显增加小鼠海马区神经元数目(P0.05),对模型小鼠海马区神经元有明显的保护作用。结论:(1)AE-624对LPS诱导的PC12细胞损伤有明显的保护作用。(2)AE-624对链脲佐菌素(STZ)诱导的AD模型小鼠认知功能具有明显保护作用,其保护作用机制可能与AE-624的抗氧化作用、抗神经元凋亡以及提高小鼠海马PP-DG区的LTP,改善模型小鼠突触可塑性有关。
[Abstract]:Aim: to investigate the protective effect of AE-624 on PC12 cell injury induced by LPS at cell level. The effects of AE-624 on the cognitive behavior of AD model mice induced by streptozotocin (STZ) lateral ventricle injection were studied at the animal level, and the related mechanisms were discussed. Methods: (1) PC12 cells were induced by 200 渭 g / mL LPS, and the cells were antagonized by AE-624 of 50 渭 g / mL. The survival rate of each group was detected by (MTT). (2) Kunming mice or BALB/c mice were randomly divided into normal group and model group according to their body weight. The positive control group (Donepezil group) had low, medium and high dose AE 624. With the exception of normal mice, the other groups were injected with STZ (30 渭 g / 渭 L, 5 渭 L) to make AD model. Then the rats were given a 45 mg / kg AE-624 solution for 15 days. After administration, the cognitive behavior of mice was tested by behavioral experiments such as self-activity, new object recognition, water maze and so on. The effect of AE-624 on synaptic plasticity was observed by LTP experiment. The effect of AE-624 on oxidation was observed by measuring the activity of SOD in serum and hippocampal tissue, and the effect of AE-624 on mouse neurons was observed by Nissl staining. Results: (1) the cell survival rate of AE-624 group was significantly higher than that of model group (P0.05 or P0.005), which indicated that it had obvious protective effect on PC12 cell injury induced by LPS. (2) compared with model group, the cognitive behavior of mice in AE-624 group was significantly higher than that in model group (P0.05 or P0.005). Increased autonomous activity (P0.05), increased priority index for new object recognition (P0.05), increased time to open arms in the O maze (P0.05 or P0.01), significantly shortened escape latency during water maze testing (P0.01 or P0.005) .LTP significantly increased the administration of the drug: AE-624. The increase of PS wave in the model group was significantly higher than that in the model group (P0.05). Compared with the normal group, the activity of SOD in serum and hippocampus of the model group was significantly decreased (P0.05). Compared with the model group, the AE-624 group significantly increased the activity of SOD in serum and hippocampus (P0.05 or P0.001), and decreased the content of MDA in serum and hippocampus (P0.05 or P0.001). Nissl staining showed that the number of neurons in the model group was significantly lower than that in the normal group (P0.01), and the number of neurons in the hippocampal area of the model group was significantly increased (P0.05) compared with the model group, which had obvious protective effect on the hippocampal neurons of the model mice. Conclusion: (1) AE-624 has obvious protective effect on PC12 cell injury induced by LPS. (2) AE-624 has obvious protective effect on cognitive function of AD model mice induced by streptozotocin (STZ), and its protective mechanism may be related to the antioxidant effect of AE-624. Anti-neuronal apoptosis and improving the synaptic plasticity of model mice by increasing LTP, in the PP-DG region of hippocampus were related.
【学位授予单位】：新疆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285.5;R-332

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