天泰1号对自发阿尔茨海默病鼠海马CA1区分子层突触可塑性的影响 超微结构定量研究(英文)

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背景:中枢神经的突触可塑性是行为依赖性学习记忆的核心基础,治疗阿尔茨海默病的天然中药是否通过增加突触可塑性来改善学习记忆尚罕见报道。目的押观察天泰1号对自发阿尔茨海默病模型学习记忆功能及神经突触可塑性的影响。设计:随机对照实验。单位:深圳市中西医结合研究所。材料:实验在深圳市中西医结合临床研究所二级动物实验室完成。实验动物为昆明种小鼠。方法押从21个月龄昆明种小鼠筛选出自发阿尔茨海默病(记忆障碍)鼠52只,随机分为4组即老年痴呆组、西药对照组、天泰1号6.80g/kg组、天泰1号20.41g/kg组,另设13只老年学习记忆正常鼠为老年正常组。西药对照组给以甲磺酸二氢麦角碱0.6mg/kg,天泰1号6.80g/kg,20.41g/kg组分别予天泰1号方6.80g/kg及20.41g/kg,以上均研配成0.5mL液体灌胃给药,连续60d,老年正常组和老年痴呆组均灌以等量双蒸水。用跳台实验检测学习记忆成绩鸦海马CA1区脑组织超薄切片,透射电镜观察,并全自动显微图像分析系统定量检测突触可塑性参数。主要观察指标:①天泰1号不同剂量对自发阿尔茨海默病鼠学习记忆的影响。②突触电镜观察及体视学定量检测结果。结果押实验过程中实验动物无脱失,均进入结果分析。①天泰1号不同剂量对自发阿尔茨海默病鼠学习记忆的影响:天泰1号6.80g/kg组,20.41g/kg组的学习、记忆错误次数均小于老年痴呆组,且天泰1号20.41g/kg组的学习、记忆错误次数小于天泰1号6.80g/kg组;天泰1号6.80g/kg组,20.41g/kg组的学习训练逃避潜伏期小于老年痴呆组,记忆测试安全平台潜伏期大于老年痴呆组,且天泰1号20.41g/kg组的记忆测试安全平台潜伏期大于天泰1号6.80g/kg组。②突触电镜观察及体视学定量检测:与老年正常鼠相比,老年痴呆鼠出现突触数明显减少,部分突触间隙模糊不清,突触连接间断,突触小泡大小不等等变性现象,其余各组也可见突触变性改变,但程度较模型组轻。天泰1号可明显增高其海马CA1区分子层突触的数密度和面密度,且天泰1号20.41g/kg组所增高的幅度大于天泰1号6.80g/kg组。结论押天泰1号可明显改善自发阿尔茨海默病模型鼠的学习记忆障碍,这一作用可能与其促进突触再生,改善其大脑的突触可塑性有关,其作用呈现出一定的量效关系。 Background: Synaptic plasticity of the central nervous system is the core of behavior-dependent learning and memory. It is still rare to report whether natural Chinese medicines for Alzheimer’s disease improve learning and memory by increasing synaptic plasticity. Objective To observe the effect of Tiantai No. 1 on learning and memory function and synaptic plasticity of spontaneous Alzheimer’s disease model. Design: Randomized controlled trials. Unit: Shenzhen Institute of Integrative Medicine. MATERIALS: Experiments were performed at the Class II Animal Laboratory of the Institute of Integrated Chinese and Western Medicine in Shenzhen. The experimental animals were Kunming mice. Methods A total of 52 spontaneous Alzheimer’s disease (memory impairment) mice were selected from 21-month-old Kunming mice and randomly divided into 4 groups: Alzheimer’s disease group, Western medicine control group, Tiantai No. 1 group, 6.80 g/kg group. , Tiantai No. 1 20.41g/kg group, another set of 13 elderly normal learning and memory mice for the elderly normal group. Western medicine control group was given 0.6 mg/kg of dihydroergotoxine mesylate, 6.80 g/kg of Tiantai No.1, and 20.41 g/kg respectively in the 20.41 g/kg group and Tiantai No.1 6.80 g/kg and 20.41 g/kg respectively. The rats were given intragastric administration with 0.5 mL of liquid for 60 days. The elderly normal and senile dementia groups were administrated with the same amount of double distilled water. Using a step-down experiment to detect learning and memory scores, brain tissue ultra-thin section of CA1 hippocampus, transmission electron microscope observation, and automatic microscopic image analysis system quantitative detection of synaptic plasticity parameters. MAIN OUTCOME MEASURES: The effect of different doses of Tiantai No. 1 on learning and memory of rats with spontaneous Alzheimer’s disease. 2 Synapse electron microscopy and stereological quantitative detection results. The experimental animals did not get lost during the test, and all the results were analyzed. 1 Effect of different doses of Tiantai No.1 on learning and memory in rats with spontaneous Alzheimer’s disease: Tiantai No. 1 in the 6.80g/kg group, 20.41g/kg group had fewer learning and memory errors than the Alzheimer’s disease group, and Tiantai The number of learning and memory errors in the No.1 20.41g/kg group was less than the 6.80g/kg group in the Tiantai No.1 group; the escape latency in the learning and training of the Tiantai No.1 6.80g/kg group was lower than that in the dementia group in the 20.41g/kg group. The incubation period of the test safety platform was greater than that of the Alzheimer’s group, and the latency period of the memory test safety platform of the Tiantai No.1 20.41g/kg group was greater than that of the Tiantai No.1 6.80g/kg group. 2 Synaptic electron microscopy and stereological quantification: The senile dementia rats had significantly reduced synapse number, blurred synaptic space, intermittent synaptic connections, and small synaptic vesicles, compared with aged normal mice. Degeneration phenomenon, the remaining groups also showed changes in synaptic degeneration, but the degree of lighter than the model group. Tiantai 1 can significantly increase the number density and areal density of synapses in the hippocampal CA1 region, and the increase in Tiantai No.1 20.41g/kg group is greater than Tiantai No.1 6.80g/kg group. Conclusion Bentiantai 1 can significantly improve learning and memory impairment in rats with spontaneous Alzheimer’s disease. This effect may be related to its promotion of synaptic regeneration and improvement of synaptic plasticity in the brain, and its effect shows a dose-effect relationship. .
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