2-(α-羟基戊基)苯甲酸盐对痴呆大鼠大脑皮质、海马微细结构的影响
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摘要
目的探讨2-(α-羟基戊基)苯甲酸盐(HPB)对痴呆大鼠大脑皮质、海马微细结构的影响。方法 SD健康大鼠72只,其中60只被联合采用D-半乳糖、亚硝酸钠及三氯化铝复制为大鼠痴呆模型,并随机分为模型组、多奈哌齐组、HPB 15 mg/kg组、HPB 45 mg/kg组、HPB 135 mg/kg组,每组12只;另12只正常大鼠作为对照组。3个HPB组分别给予相应剂量的HPB灌胃给药,每天1次,连续30 d,第30天处死动物、取材。采用水迷宫测试各组大鼠的行为学,ELISA法检测脑组织sAPPα、Aβ42含量,HE染色和改良Bielschowsky氨银液染色观察大鼠大脑皮质、海马微细结构的变化。结果与对照组比较,模型组平均潜伏期(IP)、第一次穿越原平台位置的时间(FTAPT)明显延长,在原平台象限活动的时间(TAOP)明显缩短;与模型组比较,HPB 45 mg/kg组、HPB 135 mg/kg组、多奈哌齐组大鼠的IP、FTAPT缩短,TAOP延长,差异均有统计学意义(P<0.05);与对照组比较,模型组大鼠的脑组织sAPPα含量降低、Aβ42含量升高;与模型组比较,HPB 45 mg/kg组、HPB 135 mg/kg组、多奈哌齐组大鼠的脑组织sAPPα含量升高,但Aβ42含量降低,差异均有统计学意义(P<0.05);HE染色结果显示,模型组大鼠海马CA3区神经元排列不整齐、数量少,细胞小、结构模糊、核固缩;HPB 135 mg/kg组大鼠海马CA3区神经元排列较整齐、数量增多,结构较清晰;改良Bielschowsky氨银液染色结果显示,模型组皮质神经元体积小、数量少,排列分散、层次不清,皮质神经元之间、皮质与海马之间神经纤维细而稀疏;HPB 135 mg/kg组大鼠脑皮质神经元体积明显变大、数量明显增多,排列较整齐,皮质与海马之间神经纤维较多。结论 HPB对痴呆大鼠大脑皮质、海马微细结构有一定的改善作用,从而提高其空间学习记忆能力;其机制可能与HPB提高痴呆鼠脑组织sAPPα表达、降低Aβ42表达有关。
Objective To investigate the effects of 2-(α-hydroxyamyl) benzoate(HPB) on the fine structure of cerebral cortex and hippocampus in dementia rats. Methods Seventy-two SD healthy rats were selected. Sixty of them were treated with D-galactose, sodium nitrite and aluminum trichloride to establish dementia models, which were randomly divided into model group, donepezidine group, HPB 15 mg/kg group, HPB 45 mg/kg group, and HPB 135 mg/kg group, with 12 rats in each group, and another 12 normal rats served as the control group. The rats in three HPB groups were given corresponding dose of HPB by gavage once a day for 30 days, and the animals were killed on the 30 th day to collect samples. The behavior of each group was tested by water maze. The contents of s APPα and Aβ42in brain tissue were measured by ELISA method. The changes in the fine structure of cerebral cortex and hippocampus were observed by HE staining and modified Bielschowsky ammonia silver staining. Results Compared with the control group, the average incubation period(IP) and the time to cross the original platform position for the first time(FTAPT) in the model group were significantly prolonged, and the time to move in the original platform quadrant(TAOP) was significantly shortened. Compared with the model group, IP and FTAPT of rats in the HPB 45 mg/kg group, HPB 135 mg/kg group and donepezil group were shortened, but TAOP is extended, with statistically significant differences(P<0.05). Compared with the control group, the content of sAPPα in the brain tissue of the model group decreased and the content of Aβ42increased. Compared with the model group, the content of sAPPα in the brain tissue of rats in the HPB 45 mg/kg group,HPB 135 mg/kg group and Donepezil group increased, but the content of Aβ42decreased, and the differences were statistically significant(P<0.05). The results of HE staining showed that neurons in the CA3 area of the hippocampus of rats in the model group were not orderly arranged, the number was small, the cells were small, the structure was fuzzy, and the nuclei shrank; in the HPB 135 mg/kg group, the neurons in the hippocampal CA3 area were orderly arranged, the number of neurons increased, and the structure was clear. The results of modified Bielschowsky's ammonia silver solution staining showed that cortical neurons in the model group were small in size, few in number, scattered in arrangement and unclear in hierarchy. Nerve fibers between cortical neurons and between cortex and hippocampus were thin and sparse. In the HPB 135 mg/kg group, the neurons in the cerebral cortex became larger and more numerous, and arranged neatly, and there were more nerve fibers between the cortex and hippocampus. Conclusion HPB can improve the fine structure of cerebral cortex and hippocampus of dementia rats to improve their spatial learning and memory ability, and its mechanism may be related to the increase of sAPPα expression and the decrease of Aβ42expression in the brain tissue of dementia rats by HPB.
Objective To investigate the effects of 2-(α-hydroxyamyl) benzoate(HPB) on the fine structure of cerebral cortex and hippocampus in dementia rats. Methods Seventy-two SD healthy rats were selected. Sixty of them were treated with D-galactose, sodium nitrite and aluminum trichloride to establish dementia models, which were randomly divided into model group, donepezidine group, HPB 15 mg/kg group, HPB 45 mg/kg group, and HPB 135 mg/kg group, with 12 rats in each group, and another 12 normal rats served as the control group. The rats in three HPB groups were given corresponding dose of HPB by gavage once a day for 30 days, and the animals were killed on the 30 th day to collect samples. The behavior of each group was tested by water maze. The contents of s APPα and Aβ42in brain tissue were measured by ELISA method. The changes in the fine structure of cerebral cortex and hippocampus were observed by HE staining and modified Bielschowsky ammonia silver staining. Results Compared with the control group, the average incubation period(IP) and the time to cross the original platform position for the first time(FTAPT) in the model group were significantly prolonged, and the time to move in the original platform quadrant(TAOP) was significantly shortened. Compared with the model group, IP and FTAPT of rats in the HPB 45 mg/kg group, HPB 135 mg/kg group and donepezil group were shortened, but TAOP is extended, with statistically significant differences(P<0.05). Compared with the control group, the content of sAPPα in the brain tissue of the model group decreased and the content of Aβ42increased. Compared with the model group, the content of sAPPα in the brain tissue of rats in the HPB 45 mg/kg group,HPB 135 mg/kg group and Donepezil group increased, but the content of Aβ42decreased, and the differences were statistically significant(P<0.05). The results of HE staining showed that neurons in the CA3 area of the hippocampus of rats in the model group were not orderly arranged, the number was small, the cells were small, the structure was fuzzy, and the nuclei shrank; in the HPB 135 mg/kg group, the neurons in the hippocampal CA3 area were orderly arranged, the number of neurons increased, and the structure was clear. The results of modified Bielschowsky's ammonia silver solution staining showed that cortical neurons in the model group were small in size, few in number, scattered in arrangement and unclear in hierarchy. Nerve fibers between cortical neurons and between cortex and hippocampus were thin and sparse. In the HPB 135 mg/kg group, the neurons in the cerebral cortex became larger and more numerous, and arranged neatly, and there were more nerve fibers between the cortex and hippocampus. Conclusion HPB can improve the fine structure of cerebral cortex and hippocampus of dementia rats to improve their spatial learning and memory ability, and its mechanism may be related to the increase of sAPPα expression and the decrease of Aβ42expression in the brain tissue of dementia rats by HPB.
引文
[1]胡艳丽. 2-(α-羟基戊基)苯甲酸钾盐的神经保护作用及对AD转基因小鼠的作用[D].北京:北京协和医学院, 2010.
[2]赵万红. 2-(α-羟基戊基)苯甲酸钾盐对痴呆动物模型的治疗作用及其机制研究[D].北京:中国协和医科大学, 2008.
[3]姚柏春,敖云,张戈,等.绞股蓝皂甙对痴呆小鼠学习记忆能力影响及机制[J].中国公共卫生, 2017, 33(12):1708-1711.
[4]陈晨,吴泽青,陈秋荷,等.散发性阿尔茨海默病动物模型研究进展[J].药学研究, 2018, 37(2):63-71, 83.
[5]段良霞,景晓芬.中国老年人口迁移特征及原因分析—基于第六次全国人口普查数据[J].老龄科学研究, 2018, 6(4):31-39.
[6]陈智雅,张研.阿尔茨海默病发病机制研究概述[J].基础医学与临床, 2018, 38(3):289-293.
[7]瞿千千,张文霞,卢燕婉,等. 20例阿尔茨海默病患者海马代谢磁共振波谱检测探讨[J].上海医药, 2018, 39(15):55-56, 69.
[8]孔莹,李雪岩,包瑞,等.针刺百会穴对阿尔茨海默病模型大鼠海马区Aβ42影响[J].辽宁中医药大学学报, 2018, 20(8):126-129.
[9]金昊. APP/PS1小鼠不同时期内嗅皮质、海马体积变化特征及对学习记忆能力的影响[D].福州:福建中医药大学, 2018.
[10]李萍萍. 2-(α-羟基戊基)苯甲酸钾盐对学习记忆的改善作用及其影响长时程增强的机制研究[D].北京:北京协和医学院, 2011.
[11]赵傲楠,李彬寅,陈燕,等.阿尔茨海默病中视觉障碍与海马体积相关性研究[J].神经药理学报, 2018, 8(2):56-57.
[12]孔海龙,韦旭,周倩,等.针药结合对阿尔茨海默病模型大鼠海马CA1区ChAT、AChE表达的影响[J].皖南医学院学报, 2018, 37(4):310-313.
[13]田仰华,余永强,汪凯.基于海马亚区的阿尔茨海默病磁共振结构和功能连接研究[J].安徽医科大学学报, 2018, 53(9):1422-1426.
[14]方玲娟,严依军.盐酸多奈哌齐治疗阿尔茨海默病的临床疗效分析[J].中国神经免疫学和神经病学杂志, 2018, 25(4):271-273.
[15] LI Q, HE S, CHEN Y, et al. Donepezil-based multi-functional cholinesterase inhibitors for treatment of Alzheimer's disease[J]. European Journal of Medicinal Chemistry, 2018, 158(5):463-477.
[16]董阳婷.氧化应激在β-淀粉样蛋白及氟化物引起的实验性中枢神经损伤病理过程中的作用及其分子机制[D].贵阳:贵州医科大学,2018.
[17]徐菁,陈生弟.阿尔茨海默病中Tau蛋白和Aβ相互作用的研究进展[J].中国神经精神疾病杂志, 2014, 40(4):251-254.
[2]赵万红. 2-(α-羟基戊基)苯甲酸钾盐对痴呆动物模型的治疗作用及其机制研究[D].北京:中国协和医科大学, 2008.
[3]姚柏春,敖云,张戈,等.绞股蓝皂甙对痴呆小鼠学习记忆能力影响及机制[J].中国公共卫生, 2017, 33(12):1708-1711.
[4]陈晨,吴泽青,陈秋荷,等.散发性阿尔茨海默病动物模型研究进展[J].药学研究, 2018, 37(2):63-71, 83.
[5]段良霞,景晓芬.中国老年人口迁移特征及原因分析—基于第六次全国人口普查数据[J].老龄科学研究, 2018, 6(4):31-39.
[6]陈智雅,张研.阿尔茨海默病发病机制研究概述[J].基础医学与临床, 2018, 38(3):289-293.
[7]瞿千千,张文霞,卢燕婉,等. 20例阿尔茨海默病患者海马代谢磁共振波谱检测探讨[J].上海医药, 2018, 39(15):55-56, 69.
[8]孔莹,李雪岩,包瑞,等.针刺百会穴对阿尔茨海默病模型大鼠海马区Aβ42影响[J].辽宁中医药大学学报, 2018, 20(8):126-129.
[9]金昊. APP/PS1小鼠不同时期内嗅皮质、海马体积变化特征及对学习记忆能力的影响[D].福州:福建中医药大学, 2018.
[10]李萍萍. 2-(α-羟基戊基)苯甲酸钾盐对学习记忆的改善作用及其影响长时程增强的机制研究[D].北京:北京协和医学院, 2011.
[11]赵傲楠,李彬寅,陈燕,等.阿尔茨海默病中视觉障碍与海马体积相关性研究[J].神经药理学报, 2018, 8(2):56-57.
[12]孔海龙,韦旭,周倩,等.针药结合对阿尔茨海默病模型大鼠海马CA1区ChAT、AChE表达的影响[J].皖南医学院学报, 2018, 37(4):310-313.
[13]田仰华,余永强,汪凯.基于海马亚区的阿尔茨海默病磁共振结构和功能连接研究[J].安徽医科大学学报, 2018, 53(9):1422-1426.
[14]方玲娟,严依军.盐酸多奈哌齐治疗阿尔茨海默病的临床疗效分析[J].中国神经免疫学和神经病学杂志, 2018, 25(4):271-273.
[15] LI Q, HE S, CHEN Y, et al. Donepezil-based multi-functional cholinesterase inhibitors for treatment of Alzheimer's disease[J]. European Journal of Medicinal Chemistry, 2018, 158(5):463-477.
[16]董阳婷.氧化应激在β-淀粉样蛋白及氟化物引起的实验性中枢神经损伤病理过程中的作用及其分子机制[D].贵阳:贵州医科大学,2018.
[17]徐菁,陈生弟.阿尔茨海默病中Tau蛋白和Aβ相互作用的研究进展[J].中国神经精神疾病杂志, 2014, 40(4):251-254.