梓醇对阿尔茨海默病的保护作用研究
发布时间：2019-06-02 15:59
【摘要】：目的：观察梓醇对APP/PS1双转基因阿尔茨海默病(Alzheimer'sDisease, AD)模型鼠空间学习记忆能力和自主活动的影响以及脑内老年斑的产生、神经元丢失等典型病理特征的影响，并探讨梓醇发挥作用的相关机制，为AD的防治提供新的思路。 方法：将3月龄的APP/PS1双转基因小鼠按照随机数字表法随机分为梓醇治疗组和生理盐水对照组，每组20只，并以10只同月龄的具有相同遗传背景的C57小鼠作为正常对照，用梓醇(每天5mg/kg)和等量生理盐水腹腔注射AD模型小鼠3周，应用Morris水迷宫、旷场实验和高架十字迷宫(elevated plus maze, EPM)检测小鼠空间学习记忆能力、自主活动和焦虑情绪的变化；应用免疫组织化学检测各组小鼠脑内老年斑与神经元数量等的变化；通过Western blot检测梓醇对小鼠脑内β分泌酶活性及血管内皮生长因子(VEGF)等的影响。 结果：(1)行为学结果显示：①在Morris水迷宫实验中，3组小鼠在可视平台中找到平台的平均潜伏期和搜索的平均路径无明显差异(P0.05)；隐蔽平台实验中，梓醇治疗组小鼠找到平台的平均时间与搜索的平均距离较生理盐水对照组小鼠明显缩短(P0.01)，与正常对照组比较，无明显差异(P0.05)；在探索实验中，60s内梓醇治疗组小鼠穿越平台次数明显高于生理盐水对照组(P0.01)；②在旷场实验中，，梓醇治疗组小鼠在中央区域停留的时间和路程显著低于生理盐水对照组(P0.01)；③在高架十字迷宫实验中，3组小鼠在总的穿臂次数和时间上没有显著差别(P0.05)，梓醇治疗组小鼠穿越开臂的次数和停留在开臂上的时间要显著的高于生理盐水对照组(P0.01)，而与正常对照组相比，无显著差异(P0.05)。(2)形态学检测结果：免疫组化的结果分析显示，与生理盐水对照组相比，梓醇对照组小鼠大脑皮质和海马区域老年斑数量明显减少(P0.01)，神经元、神经元前体细胞以及血管数量明显增多，凋亡细胞显著减少。(3)蛋白水平测定结果：Western blot结果显示，与生理盐水对照组相比，梓醇治疗组小鼠脑组织中APP全蛋白的表达无明显变化，BACE1的表达显著减少(P0.01)，同时突触相关蛋白PSD95蛋白与血管内皮生长因子(VEGF)的表达显著增多(P0.01)。 结论：梓醇可显著提高APP/PS1双转基因小鼠的空间学习记忆能力，缓解其焦虑情绪与自主活动；梓醇可显著减少APP/PS1双转基因小鼠脑内Aβ的沉积与老年斑的数量，可能是通过抑制APP代谢过程中BACE1的活性，加强血管的对Aβ清除来实现的；梓醇通过抑制神经细胞的凋亡，同时促进神经元再生，减少了AD模型鼠脑内神经元与突触的丢失
[Abstract]:Objective: to observe the effect of catalpol on spatial learning and memory ability and autonomic activity in APP/PS1 double transgenic Alzheimer's disease (Alzheimer'sDisease, AD) model mice, as well as the production of aging plaques and the loss of neurons in the brain. The related mechanism of catalpol was discussed to provide a new idea for the prevention and treatment of AD. Methods: three months old APP/PS1 double transgenic mice were randomly divided into catalpol treatment group (n = 20) and saline control group (n = 20), and 10 C57 mice with the same genetic background were used as normal control. AD model mice were intraperitoneally injected with catalpol (5mg/kg per day) and the same amount of saline for 3 weeks. Morris water maze, open field test and elevated cross maze (elevated plus maze, EPM) were used to detect the spatial learning and memory ability of mice. The changes of autonomous activity and anxiety; The changes of aging plaques and the number of neurons in the brain of mice in each group were detected by immunohistochemistry, and the effects of catalpol on 尾 secretase activity and vascular endothelial growth factor (VEGF) in the brain of mice were detected by Western blot. Results: (1) the results of behavior showed that: (1) in the Morris water maze test, there was no significant difference in the average latency of finding the platform and the average path of searching in the visual platform of the three groups (P 0.05). In the hidden platform experiment, the average time of finding the platform and the average distance of search in the catalpol treatment group were significantly shorter than those in the saline control group (P 0.01), but there was no significant difference between the catalpol treatment group and the normal control group (P 0.05). In the exploration experiment, the number of mice crossing the platform in the 60 s catalpol treatment group was significantly higher than that in the saline control group (P 0.01). (2) in the open field experiment, the stay time and distance in the central area of the catalpol treatment group were significantly lower than those of the saline control group (P 0.01). (3) in the elevated cross maze test, there was no significant difference in the total number and time of arm piercing among the three groups (P 0.05). The frequency of crossing the open arm and the time of staying on the open arm in the catalpol treatment group were significantly higher than those in the saline control group (P 0.01), but compared with the normal control group, There was no significant difference in morphology (P 0.05). (2). The results of Immunohistochemical analysis showed that the number of aged plaques in cerebral cortex and hippocampus of catalpol control group was significantly lower than that of saline control group (P01), and the number of aged plaques in cerebral cortex and hippocampus of catalpol control group was significantly lower than that of saline control group. The number of neurons, neuronal progenitor cells and blood vessels increased significantly, while apoptotic cells decreased significantly. (3): Western blot results showed that compared with saline control group, the results of protein level assay showed that the number of neurons, neuronal progenitor cells and blood vessels was significantly increased and apoptotic cells were significantly decreased. In catalpol treatment group, the expression of APP whole protein in brain tissue did not change significantly, but the expression of BACE1 decreased significantly (P01), while the expression of synaptic related protein PSD95 protein and vascular endothelial growth factor (VEGF) increased significantly (P01). Conclusion: catalpol can significantly improve the spatial learning and memory ability of APP/PS1 double transgenic mice and alleviate their anxiety and autonomous activity. Catalpol can significantly reduce the deposition of A 尾 and the number of aged plaques in the brain of APP/PS1 double transgenic mice, which may be realized by inhibiting the activity of BACE1 in the process of APP metabolism and strengthening the clearance of A 尾 by blood vessels. Catalpol reduces the loss of neurons and synapses in the brain of AD model mice by inhibiting the apoptosis of nerve cells and promoting the regeneration of neurons.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.16
本文编号：2491240
[Abstract]:Objective: to observe the effect of catalpol on spatial learning and memory ability and autonomic activity in APP/PS1 double transgenic Alzheimer's disease (Alzheimer'sDisease, AD) model mice, as well as the production of aging plaques and the loss of neurons in the brain. The related mechanism of catalpol was discussed to provide a new idea for the prevention and treatment of AD. Methods: three months old APP/PS1 double transgenic mice were randomly divided into catalpol treatment group (n = 20) and saline control group (n = 20), and 10 C57 mice with the same genetic background were used as normal control. AD model mice were intraperitoneally injected with catalpol (5mg/kg per day) and the same amount of saline for 3 weeks. Morris water maze, open field test and elevated cross maze (elevated plus maze, EPM) were used to detect the spatial learning and memory ability of mice. The changes of autonomous activity and anxiety; The changes of aging plaques and the number of neurons in the brain of mice in each group were detected by immunohistochemistry, and the effects of catalpol on 尾 secretase activity and vascular endothelial growth factor (VEGF) in the brain of mice were detected by Western blot. Results: (1) the results of behavior showed that: (1) in the Morris water maze test, there was no significant difference in the average latency of finding the platform and the average path of searching in the visual platform of the three groups (P 0.05). In the hidden platform experiment, the average time of finding the platform and the average distance of search in the catalpol treatment group were significantly shorter than those in the saline control group (P 0.01), but there was no significant difference between the catalpol treatment group and the normal control group (P 0.05). In the exploration experiment, the number of mice crossing the platform in the 60 s catalpol treatment group was significantly higher than that in the saline control group (P 0.01). (2) in the open field experiment, the stay time and distance in the central area of the catalpol treatment group were significantly lower than those of the saline control group (P 0.01). (3) in the elevated cross maze test, there was no significant difference in the total number and time of arm piercing among the three groups (P 0.05). The frequency of crossing the open arm and the time of staying on the open arm in the catalpol treatment group were significantly higher than those in the saline control group (P 0.01), but compared with the normal control group, There was no significant difference in morphology (P 0.05). (2). The results of Immunohistochemical analysis showed that the number of aged plaques in cerebral cortex and hippocampus of catalpol control group was significantly lower than that of saline control group (P01), and the number of aged plaques in cerebral cortex and hippocampus of catalpol control group was significantly lower than that of saline control group. The number of neurons, neuronal progenitor cells and blood vessels increased significantly, while apoptotic cells decreased significantly. (3): Western blot results showed that compared with saline control group, the results of protein level assay showed that the number of neurons, neuronal progenitor cells and blood vessels was significantly increased and apoptotic cells were significantly decreased. In catalpol treatment group, the expression of APP whole protein in brain tissue did not change significantly, but the expression of BACE1 decreased significantly (P01), while the expression of synaptic related protein PSD95 protein and vascular endothelial growth factor (VEGF) increased significantly (P01). Conclusion: catalpol can significantly improve the spatial learning and memory ability of APP/PS1 double transgenic mice and alleviate their anxiety and autonomous activity. Catalpol can significantly reduce the deposition of A 尾 and the number of aged plaques in the brain of APP/PS1 double transgenic mice, which may be realized by inhibiting the activity of BACE1 in the process of APP metabolism and strengthening the clearance of A 尾 by blood vessels. Catalpol reduces the loss of neurons and synapses in the brain of AD model mice by inhibiting the apoptosis of nerve cells and promoting the regeneration of neurons.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.16
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