脑灵汤对Alzheimer病模型鼠海马CA3区域α4NachR和α7NachR表达的影响
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摘要
目的：探讨脑灵汤对阿尔茨海默病(Alzheimer's,AD)模型大鼠学习记忆、病理形态及其对海马CA3区α4NachR和α7NachR表达的影响,并揭示AD发病的部分机理和为寻找中医药治疗AD提供可能的理论基础。
方法：选用清洁级SD大鼠经Y-迷宫测试后,选取30只,随机分为正常组、假手术组、模型组、西药组(多耐派齐组)和中药组(脑灵汤组),每组6只,喂养一周后,采用Apl-42注射大鼠海马法制成大鼠模型,再喂养30天,治疗后用Y-迷宫试验和Morris水迷宫检测大鼠学习记忆行为能力,用刚果红染色观察大鼠海马部位p-淀粉样蛋白沉积的情况,HE染色检测大鼠海马组织形态学变化。免疫组化法观察α4NachR、α7NachR在大鼠海马CA3区中的表达。
结果：1.Y-迷宫实验中,模型组大鼠所需的电击次数最多,与假手术组和正常组比较p<0.05,中药组、西药组两组大鼠所需的电击次数减少,与模型组相比p<0.05,且两治疗组相比无显著性差异(p>0.05)。2.Morris水迷宫隐匿平台搜索实验中,与假手术组和正常组比较,模型组大鼠表现为逃避潜伏期明显延长(p<0.01)；探索实验中,正常组和假手术组动物的平均穿越次数最多,中药组和西药组动物穿越次数又多于模型组,比较有显著差异(p<0.01)。3.刚果红染色：正常组、假手术组大鼠海马切片在光镜下未见橘红色淀粉样沉积。模型组大鼠的海马切片上可见橘红色斑块状淀粉样沉积,说明模型组海马组织区有Ap沉淀。4.光镜观察显示,假手术组和正常组大鼠海马CA3区锥体细胞排列紧密整齐；模型组大鼠海马CA3区锥体细胞排列紊乱,有细胞缺失的现象,且正常锥体细胞数目较正常组和假手术组比较明显减少(p<0.05)；两治疗组大鼠海马CA3区锥体细胞形态较模型组正常,排列较整齐,缺失的细胞少,更接近假手术组。5.α4NachR免疫组化结果显示,模型组大鼠海马CA3区域阳性细胞数最少,染色最浅。6.α7NachR免疫组化结果显示,各组大鼠海马CA3区α7NachR阳性细胞数比较,模型组最少,染色浅,正常组阳性细胞数最多,染色最深,而中药组、西药组阳性细胞数介于正常组及模型组之间。
结论：1.本实验研究中,采用Ap1-42注射大鼠海马制作的AD模型大鼠出现了AD的一些行为学和病理改变,说明成功建立了AD模型。2.AD模型大鼠的行为学能力明显下降,脑灵汤能改善模型大鼠的行为学能力。3.脑灵汤通过上调AD模型大鼠海马CA3区细胞膜上α7NachR、α4NachR的表达来达到预防和治疗AD的作用。
OBJECTIVE:To observe the effect of Naoling Decoction on ethology, hippocamal histomorphology,and expression of a4NachR and a7NachR in CA3 region of the rats with the model Alzheimer disease, and explore the therapeutical effect on Alzheimer disease rats and the potential mechanism of action of Naoling Decoction.
METHODS:After Y-electric-maze testing,chooseing thirty SD (spragu-dawleg) rats were classified into five groups:normal group, sham-operated group, model group,western medical group(donepezil group) and traditional Chinese drug group(Naoling Decoctio group). The Alzheimer disease model was established by Aβ1-42 injected into hippocamal in rats. The faculty of learning and memory was evaluated by Y-electric-maze test and Morris water maze experiment.The brain tissues were removed to be made frozen sections and stained with congored to detect the aggradation of Aβ,the changes of cell morphology were detected by HE stain. Expression of a4-NachR and a7-NachR in CA3 region was measured with immunohistochemical staining.
RESULTS:1.The results of Y-electric-maze test showed that compared with sham-operated group and normal group, model group's times to evade stimulate is more (P<0.05);compared with model group, Naoling Decoctio group and Piracetam group's times to evade stimulate is less(p<0.05). Meanwhile, there existed no obvious difference between these two therapy groups(p>0.05).2. The results of Morris water maze experiment showed that Compared with sham-operated group and normal group, the escaped and latent period of model group was delayed significantly (P<0.05). In exploratory experiment, the average pass through times in sham operation group and normal group were more than that of other three ones, and that of the model group was lest, there were significant difference (P<0.05). 3.Congored coloration result:Under the light microscope,in the hippocampal fields of rats in sham-operated group and normal group,orange amylaceous aggradation can’t be seen, the cells in DG arrange in order. In the hippocampal fields of rats in the model group, significant orange amylaceous aggradation can be seen in the area that injecting Aβ1-42,this denota there is aggradation of Aβin the hippocampal fields of rats in the model group,meanwhile,the cells in DG obviously damaged,neuron loss noticeable,and there is neuroglial cell proliferation.4.Under the light microscope, hippocampal CA3 fields of rats in the sham-operated group and normal group exhibited closely and neatly spaced pyramidal cells, and insignificant neuron loss;in the hippocampal CA3 fields of rats in the model group sparse and disturbed pyramidal cells,noticeable neuron loss and neuroglial cell proliferation could be seen,meanwhile,the number of pyramidal cells is less than sham-operated group and normal group(p<0.05). Neuron loss reduced significantly in the hippocampal CA3 pyramidal cell fields of the two therapy group and cell morphology presented relative normal.5.The result ofα4NachR with immunohistochemical staining denote the model one'masculine cells abouta4NachR was the least in hippocampal CA3 region,and their colour are darker than theirs.6.The result of a7NachR with immunohistochemical staining denote:the normal group,masculine cells abouta7NachR was the most in hippocampal CA3 region, their colour are darkerst.The Naoling Decoctio group and donepezil group had masculine cells between the model one and the normal group。
CONCLUSIONS:1.The presentation of results of the study that the model was established by Aβ1-42 injected into hippocamal was blest, because the model rats had the changes of praxiology and pathology.2.The learning and memory of the model rats were decreased obviously, Naoling Decoction can improve the learning and memory of the model rats.3.Naoling Decoction can increase the expression ofa4NachR anda7NachR in hippocampal CA3 of AD rats.
方法：选用清洁级SD大鼠经Y-迷宫测试后,选取30只,随机分为正常组、假手术组、模型组、西药组(多耐派齐组)和中药组(脑灵汤组),每组6只,喂养一周后,采用Apl-42注射大鼠海马法制成大鼠模型,再喂养30天,治疗后用Y-迷宫试验和Morris水迷宫检测大鼠学习记忆行为能力,用刚果红染色观察大鼠海马部位p-淀粉样蛋白沉积的情况,HE染色检测大鼠海马组织形态学变化。免疫组化法观察α4NachR、α7NachR在大鼠海马CA3区中的表达。
结果：1.Y-迷宫实验中,模型组大鼠所需的电击次数最多,与假手术组和正常组比较p<0.05,中药组、西药组两组大鼠所需的电击次数减少,与模型组相比p<0.05,且两治疗组相比无显著性差异(p>0.05)。2.Morris水迷宫隐匿平台搜索实验中,与假手术组和正常组比较,模型组大鼠表现为逃避潜伏期明显延长(p<0.01)；探索实验中,正常组和假手术组动物的平均穿越次数最多,中药组和西药组动物穿越次数又多于模型组,比较有显著差异(p<0.01)。3.刚果红染色：正常组、假手术组大鼠海马切片在光镜下未见橘红色淀粉样沉积。模型组大鼠的海马切片上可见橘红色斑块状淀粉样沉积,说明模型组海马组织区有Ap沉淀。4.光镜观察显示,假手术组和正常组大鼠海马CA3区锥体细胞排列紧密整齐；模型组大鼠海马CA3区锥体细胞排列紊乱,有细胞缺失的现象,且正常锥体细胞数目较正常组和假手术组比较明显减少(p<0.05)；两治疗组大鼠海马CA3区锥体细胞形态较模型组正常,排列较整齐,缺失的细胞少,更接近假手术组。5.α4NachR免疫组化结果显示,模型组大鼠海马CA3区域阳性细胞数最少,染色最浅。6.α7NachR免疫组化结果显示,各组大鼠海马CA3区α7NachR阳性细胞数比较,模型组最少,染色浅,正常组阳性细胞数最多,染色最深,而中药组、西药组阳性细胞数介于正常组及模型组之间。
结论：1.本实验研究中,采用Ap1-42注射大鼠海马制作的AD模型大鼠出现了AD的一些行为学和病理改变,说明成功建立了AD模型。2.AD模型大鼠的行为学能力明显下降,脑灵汤能改善模型大鼠的行为学能力。3.脑灵汤通过上调AD模型大鼠海马CA3区细胞膜上α7NachR、α4NachR的表达来达到预防和治疗AD的作用。
OBJECTIVE:To observe the effect of Naoling Decoction on ethology, hippocamal histomorphology,and expression of a4NachR and a7NachR in CA3 region of the rats with the model Alzheimer disease, and explore the therapeutical effect on Alzheimer disease rats and the potential mechanism of action of Naoling Decoction.
METHODS:After Y-electric-maze testing,chooseing thirty SD (spragu-dawleg) rats were classified into five groups:normal group, sham-operated group, model group,western medical group(donepezil group) and traditional Chinese drug group(Naoling Decoctio group). The Alzheimer disease model was established by Aβ1-42 injected into hippocamal in rats. The faculty of learning and memory was evaluated by Y-electric-maze test and Morris water maze experiment.The brain tissues were removed to be made frozen sections and stained with congored to detect the aggradation of Aβ,the changes of cell morphology were detected by HE stain. Expression of a4-NachR and a7-NachR in CA3 region was measured with immunohistochemical staining.
RESULTS:1.The results of Y-electric-maze test showed that compared with sham-operated group and normal group, model group's times to evade stimulate is more (P<0.05);compared with model group, Naoling Decoctio group and Piracetam group's times to evade stimulate is less(p<0.05). Meanwhile, there existed no obvious difference between these two therapy groups(p>0.05).2. The results of Morris water maze experiment showed that Compared with sham-operated group and normal group, the escaped and latent period of model group was delayed significantly (P<0.05). In exploratory experiment, the average pass through times in sham operation group and normal group were more than that of other three ones, and that of the model group was lest, there were significant difference (P<0.05). 3.Congored coloration result:Under the light microscope,in the hippocampal fields of rats in sham-operated group and normal group,orange amylaceous aggradation can’t be seen, the cells in DG arrange in order. In the hippocampal fields of rats in the model group, significant orange amylaceous aggradation can be seen in the area that injecting Aβ1-42,this denota there is aggradation of Aβin the hippocampal fields of rats in the model group,meanwhile,the cells in DG obviously damaged,neuron loss noticeable,and there is neuroglial cell proliferation.4.Under the light microscope, hippocampal CA3 fields of rats in the sham-operated group and normal group exhibited closely and neatly spaced pyramidal cells, and insignificant neuron loss;in the hippocampal CA3 fields of rats in the model group sparse and disturbed pyramidal cells,noticeable neuron loss and neuroglial cell proliferation could be seen,meanwhile,the number of pyramidal cells is less than sham-operated group and normal group(p<0.05). Neuron loss reduced significantly in the hippocampal CA3 pyramidal cell fields of the two therapy group and cell morphology presented relative normal.5.The result ofα4NachR with immunohistochemical staining denote the model one'masculine cells abouta4NachR was the least in hippocampal CA3 region,and their colour are darker than theirs.6.The result of a7NachR with immunohistochemical staining denote:the normal group,masculine cells abouta7NachR was the most in hippocampal CA3 region, their colour are darkerst.The Naoling Decoctio group and donepezil group had masculine cells between the model one and the normal group。
CONCLUSIONS:1.The presentation of results of the study that the model was established by Aβ1-42 injected into hippocamal was blest, because the model rats had the changes of praxiology and pathology.2.The learning and memory of the model rats were decreased obviously, Naoling Decoction can improve the learning and memory of the model rats.3.Naoling Decoction can increase the expression ofa4NachR anda7NachR in hippocampal CA3 of AD rats.
引文
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[5]陈燕,赵春玲,烟碱型乙酰胆碱受体在认知功能中的作用[J].国际病理科学与临床杂志,2008,28(2)：0142-05
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