酸枣仁汤择时用药对Alzheimer病大鼠认知功能障碍的作用及可能机制

发布时间：2017-12-27 18:25

本文关键词：酸枣仁汤择时用药对Alzheimer病大鼠认知功能障碍的作用及可能机制　出处：《皖南医学院》2016年硕士论文　论文类型：学位论文

【摘要】：目的:采用酸枣仁汤卯时和酉时择时用药的方法,观察酸枣仁汤改善阿茨海默病模型大鼠认知功能障碍的疗效,并进一步探讨其作用机制。方法:选用清洁级雄性SD大鼠48只,随机分为正常组、模型组、酸枣仁汤卯时组(卯时组)、酸枣仁汤酉时组(酉时组),采用D-半乳糖和Aβ1-42双因素制备AD大鼠模型,卯时组和酉时组分别于6:00和18:00灌胃酸枣仁汤10.5g/kg,正常组与模型组每天6:00灌胃等体积的生理盐水,每周测量大鼠体温和自主活动,第42天开始对各组进行Morris水迷宫测试,第49天采血取样,Elisa法测定大鼠血清中5-HT、MT、MTR的浓度,HE染色检测大鼠海马组织形态学变化,免疫组化测定AD大鼠海马CA1区神经元细胞Taup Ser199位点阳性表达。结果:(1)水迷宫定位航行实验中,模型组大鼠逃避平台的时间明显高于正常组(P0.05),酉时组和卯时组大鼠逃避平台时间明显低于模型组(P0.05),卯时组大鼠逃避时间明显低于酉时组(P0.05);在空间探索实验中,模型组大鼠每分钟穿越隐蔽平台的次数明显少于正常组(P0.05),卯时组和酉时组大鼠每分钟穿越隐蔽平台的次数明显多于模型组(P0.05),卯时组大鼠每分钟穿越隐蔽平台的次数明显多于酉时组(P0.05)。(2)模型组大鼠血清5-HT、MT、MTR浓度明显低于正常组(P0.05),卯时组、酉时组大鼠血清5-HT、MT、MTR浓度明显高于模型组(P0.05),卯时组大鼠血清5-HT、MT、MTR浓度明显高于酉时组(P0.05)。(3)病理形态学方面:正常组大鼠海马CA1区组织细胞结构清楚,胞核圆大,着色清楚,神经元排列紧密整齐。模型组大鼠海马CA1区组织细胞结构模糊,胞核肿胀,胞核碎裂,形态不规则,大量神经元变性,核固缩。卯时组和酉时组大鼠海马CA1区组织细胞结构比较清晰,胞核肿胀和胞核碎裂减少,形态比较规则,神经元排列比较整齐,卯时组大鼠海马CA1区组织形态结构更接近正常组。(4)Tau蛋白免疫组织化学:模型组大鼠海马CA1区神经元细胞胞浆呈棕黄色,阳性表达细胞数明显高于正常组(P0.05),卯时组和酉时组大鼠海马CA1区神经元细胞胞浆呈浅棕黄色,阳性表达细胞数明显低于模型组(P0.05),卯时组大鼠海马CA1区神经元阳性表达细胞数明显低于酉时组(P0.05)。结论:(1)酸枣仁汤对AD大鼠认知功能障碍有明显改善作用。(2)不同时间点用药对AD大鼠认知功能障碍的改善作用效果不同,卯时组优于酉时组。(3)酸枣仁汤对AD大鼠认知功能的有效途径可能为通过提高AD大鼠血清中5-HT、MT、MTR浓度而改善睡眠,进而改善大鼠的认知功能。(4)酸枣仁汤能够通过降低AD大鼠脑Tau蛋白磷酸化的水平,改善大鼠的认知功能,缓解阿尔茨海默病的症状。
[Abstract]:Objective: using the medication of Suanzaoren Decoction and Mao Shi timing, observation of Suanzaoren Decoction to improve the efficacy of cognitive dysfunction in Alzheimer's disease model rats, and to explore its mechanism. Methods: the male SD 48 rats were randomly divided into normal group, model group and szrt Mao Group (Mao Shizu), Suanzaorentang group (You Shizu), when using D- galactose and A beta 1-42 dual factors of the preparation of a rat model of AD group and the group were around you 6:00 and 18:00 gavage Suanzaorentang 10.5g/kg every day, the model group and the normal group 6:00 normal saline gastric volume, weekly measurement of body temperature in rats and autonomic activities, the forty-second day on the Morris water maze test in each group, the forty-ninth day of blood sampling, Elisa determination of serum 5-HT, MT, MTR HE staining, the morphological changes of hippocampus of rats were determined by immunohistochemistry. The positive expression of AD in rat hippocampal CA1 area neurons Taup Ser199 site. Results: (1) water maze navigation experiment, model group rat escape platform time was significantly higher than the normal group (P0.05 group), and by when rats escape platform time was significantly lower than the model group (P0.05), around the rats escape latency was significantly lower than that of Shi Group (P0.05); in the space exploration experiment in the number of rats per minute through the hidden platform was less than the normal group (P0.05), the number of group and group of rats around you every minute through the hidden platform than the model group (P0.05), the number of rats per minute by crossing the hidden platform than when group (P0.05). (2) the model group rats serum 5-HT, MT, MTR concentration was significantly lower than that of normal group (P0.05), Mao Shi Shi Group, group of rats serum 5-HT, MT, MTR were significantly higher than the model group (P0.05), around the group of rats serum 5-HT, MT and MTR were significantly higher than the period group (P0.05). (3) pathomorphology: the structure of the hippocampal CA1 area of the normal group was clear, the nucleus of the nucleus was large, the coloring was clear, and the neurons were arranged closely and neatly. In the model group, the structure of the hippocampal CA1 area was blurred, the nucleus was swollen, the nucleus was broken, the shape was irregular, a large number of neurons were denatured and nuclear retracted. Around the group and when group CA1 of rat hippocampus tissue structure is clear, nuclear swelling and nuclear fragmentation reduced, comparison rules form, neurons arrangement is neat, around the group of CA1 of rat hippocampus tissue structure closer to the normal group. (4) Tau protein immunohistochemistry: model group rats hippocampus CA1 neurons in the cytoplasm was brown, positive cells was significantly higher than the normal group (P0.05 group), and group by Shi CA1 of rat hippocampus neuron cell cytoplasm was light brown, positive cells was significantly lower than the model group (P0.05), around the rats hippocampal CA1 neurons positive cells was significantly lower than that of Shi Group (P0.05). Conclusion: (1) zizzizen decoction can improve the cognitive impairment of AD rats. (2) at different time points of different medication effect on cognitive impairment of AD rats, by group group is better than you. (3) the effective way of cognitive function of Zizyphus jujube Decoction to AD rats is to improve sleep by improving the concentration of 5-HT, MT and MTR in AD rats, and then improving the cognitive function of rats. (4) zizzizzen soup can reduce the level of Tau protein phosphorylation in the brain of AD rats, improve the cognitive function of rats and alleviate the symptoms of Alzheimer's disease.
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R277.7

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