小檗碱对AD大鼠认知功能的改善及其机制的研究

发布时间：2018-03-01 02:33

本文关键词： 阿尔茨海默病小檗碱 IGF-1 IGF-1R　出处：《中南大学》2013年硕士论文　论文类型：学位论文

【摘要】：背景：中枢胰岛素抵抗与阿尔茨海默病密切相关。IGF-1在胰岛素抵抗中扮演重要作用,在AD模型鼠上增加IGF-1的表达,可以使Aβ沉积和tau蛋白磷酸化减少。研究表明小檗碱可提高IGF-1的表达,改善糖尿病鼠的认知功能。但目前小檗碱与AD模型鼠病理生理和认知功能的关系,国内外尚无文献报道。目的：建立具有中枢胰岛素抵抗的阿尔茨海默病大鼠模型,初步探讨小檗碱对阿尔茨海默病模型大鼠认知功能的改善及其可能的作用机制。方法：清洁级成年雄性SD大鼠经筛选后随机分为正常组、假手术组、模型组和干预组。采用双侧侧脑室注射链脲佐菌素建立阿尔茨海默病模型。采用Morris水迷宫检测大鼠的记忆认知功能；刚果红染色观察海马部位是否存在β-淀粉样蛋白沉积；HE染色、Nissl染色观察海马组织形态学的变化；免疫组织化学法观察海马CA3区IGF-1及IGF-1R表达的影响。结果： 1、正常组和假手术组比较：病理组织形态学改变不明显；IGF-1和IGF-1R的阳性表达细胞数无统计学差异(P0.05)。 2、AD模型组与正常组比较：刚果红染色可见橘红色斑块状物质,提示为Ap蛋白沉积；海马CA3区锥体细胞排列稀疏、紊乱,锥体细胞数目明显减少(P0.05)；海马CA3区IGF-1和IGF-1R阳性表达细胞数目减少(P0.05)；大鼠逃避潜伏期明显延长(P0.05),平均穿越平台次数减少(P0.05)。 3、小檗碱干预组与AD模型组比较：刚果红染色可见橘红色斑块状物质明显减少,海马CA3区锥体细胞排列紧凑、紊乱程度减轻,锥体细胞数目增多(P0.05)；海马CA3区IGF-1和IGF-1R阳性表达细胞数目增多(P0.05)；大鼠逃避潜伏期明显缩短(P0.05),平均穿越平台次数增多(P0.05)。结论： 1、经侧脑室内注射链脲佐菌素可成功地建立具有中枢胰岛素抵抗的阿尔茨海默病大鼠模型。 2、小檗碱通过增加大鼠海马CA3区IGF-1和IGF-1R蛋白的表达,减少Aβ蛋白沉积、减轻神经元丢失、改善锥体细胞形态,提高AD模型大鼠的认知功能。
[Abstract]:Background: central insulin resistance is closely related to Alzheimer's disease. IGF-1 plays an important role in insulin resistance and increases the expression of IGF-1 in AD mice. Berberine can increase the expression of IGF-1 and improve the cognitive function of diabetic rats. However, the relationship between berberine and pathophysiology and cognitive function of AD model rats has not been reported. Aim: to establish a rat model of Alzheimer's disease with central insulin resistance and to explore the improvement of cognitive function and the possible mechanism of berberine on Alzheimer's disease model. Methods: adult male SD rats of clean grade were randomly divided into normal group and sham operation group after screening. Model group and intervention group. The model of Alzheimer's disease was established by bilateral intracerebroventricular injection of streptozotocin. The memory and cognitive function of rats was measured by Morris water maze. Congo red staining was used to observe the presence of 尾 -amyloid deposition in hippocampus. The morphological changes of hippocampal tissue were observed by HE staining, and the expression of IGF-1 and IGF-1R in hippocampal CA3 were observed by immunohistochemical method. Results:. 1. Comparison between normal group and sham operation group: there was no significant difference in the number of IGF-1 and IGF-1R positive cells between normal group and sham operation group (P 0.05). 2Compared with normal group, Congo red staining showed orange plaques, suggesting that AP protein was deposited, pyramidal cells in hippocampal CA3 were sparse and disordered. The number of pyramidal cells was significantly decreased, the number of IGF-1 and IGF-1R positive expression cells in hippocampal CA3 region was decreased, and the escape latency of rats was significantly prolonged (P 0.05), and the average number of times of crossing the platform was decreased (P 0.05). 3Compared with AD model group, Congo red staining showed that orange plaques were decreased, pyramidal cells in hippocampal CA3 were compact, and the degree of disorder was reduced. The number of pyramidal cells increased, the number of IGF-1 and IGF-1R positive cells increased in CA3 area of hippocampus, and the escape latency of rats shortened P0.05, and the average number of crossing platform increased. Conclusion:. 1. Streptozotocin (STZ) injection via lateral ventricle can successfully establish the model of Alzheimer's disease with central insulin resistance. 2. Berberine can increase the expression of IGF-1 and IGF-1R in CA3 area of rat hippocampus, reduce the deposition of A 尾 protein, reduce the loss of neurons, improve the morphology of pyramidal cells and enhance the cognitive function of AD rats.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.16

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