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巩卓彦,黄帅阳,陈芳,盛宁,冯慧利,董云芳,任映,杨金铎,王蓬文.参枝苓口服液对App / Ps1 双转基因小鼠早期海马突触和髓鞘改变的影响[J].中国实验动物学报,2019,27(5):592~597.
参枝苓口服液对App / Ps1 双转基因小鼠早期海马突触和髓鞘改变的影响
Effect of Shenzhiling oral liquid on early hippocampal synapses and myelin sheath alterations in App / Ps1 transgenic mice
投稿时间:2019-03-15  
DOI:10. 3969 / j.issn.1005-4847. 2019. 05. 007
中文关键词:  阿尔茨海默病  参枝苓  突触  髓鞘  少突胶质细胞  超微结构  小鼠
英文关键词:Alzheimer’s disease  Shenzheling oral liquid  synapses  myelin sheath  oligodendroglia cell  ultrastructure  mice
基金项目:
作者单位E-mail
巩卓彦 北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京 100700 gongzhuoyan629@ 163.com 
黄帅阳 北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京 100700 1138507954@ qq.com 
陈芳 北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京 100700 fangxueer1027@ 126.com 
盛宁 北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京 100700  
冯慧利 北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京 100700  
董云芳 北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京 100700  
任映 北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京 100700  
杨金铎 北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京 100700  
王蓬文 北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京 100700 pw_wang@ 163.com 
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中文摘要:
      目的 通过观察3 月龄App / Ps1 双转基因小鼠早期海马CA1 区髓鞘和突触超微结构以及髓鞘特殊染色变化,判断参枝苓口服液对AD 小鼠早期神经保护作用?方法 由PrP-hAppk595N / M596L 单转基因痴呆模型小鼠及PrP-hPs1dE9 单转基因痴呆症模型小鼠杂交培育形成的App / Ps1 双转基因小鼠模型是研究阿尔茨海默病的常用疾病模型?将3 月龄App / Ps1 双转基因小鼠随机分成模型组?多奈哌齐组[0. 92 mg/ (kg·d)],参枝苓高剂量组[50 g/ (kg·d)]?参枝苓中剂量组[25 g/ (kg·d)]?参枝苓低剂量组[12. 5 g/ (kg·d)],每组9 只;另将9 只同月龄同背景C57BL/6J 小鼠为对照组?连续灌胃3 个月,实验结束后取小鼠海马CA1 区组织进行电镜切片并观察此区域髓鞘以及突触相关的超微结构,运用神经髓鞘固蓝染色法对髓鞘进行染色分析?结果 电镜下观察显示,模型组与对照组相比,小鼠海马CA1 区突触数量减少( P < 0. 01),神经元结构出现退行性改变?少突胶质细胞形态学呈凋亡前状态以及髓鞘板层结构出现显著崩解;与模型组相比,各药物干预组小鼠海马CA1 区突触数量增多( P <0. 01),神经元和少突胶质细胞形态结构较完整?染色质均匀,髓鞘板层结构明显好转?特殊染色法显示模型组较于对照组髓鞘纤维明显减少?染色变浅,各干预组髓鞘纤维分布均呈不同程度增加且染色加深?结论 参枝苓口服液可能通过增加App / Ps1 双转基因小鼠海马CA1 区突触数量以及改善髓鞘?少突胶质细胞和神经元相关结构形态来发挥AD 早期神经保护作用?
英文摘要:
      Objective To observe the early neuroprotective effect of shenzhiling oral liquid on AD mice, andto observe the effect of shenzhiling oral liquid on the ultrastructure of myelin sheath and synapse in CA1 area ofhippocampus and the changes of special staining of myelin sheath. Methods The App / Ps1 transgenic mouse model isformed by PrP-hAppk595N / M596L single transgenic dementia model mice and PrP-hPs1dE9 single transgenicdementia model mice, which is a common disease model to study Alzheimer’ s disease. The 3-month-old App / Ps1double-transgenic mice were randomly divided into the following groups (n = 9 per group): model group, donepezilgroup [0. 92 mg/ (kg·d)], shenzheling high-dose group [50 g/ (kg·d)], shenzheling medium-dose group [25 g /(kg·d)], and shenzheling low-dose group [12. 5 g/ (kg·d)]. C57BL/6J mice of the same age and background wereused as the control group. After 3 months of continuous intragastric administration, the hippocampal CA1 tissue ofmice was obtained for electron microscopic analysis, and the ultrastructural changes of myelin sheath and synapses inthis area were observed. The myelin sheath was stained and analyzed by luxol fast blue staining of nerve myelins.Results The number of synapses in the hippocampal CA1 area was decreased in the model group compared withcontrols ( P < 0. 01); the structure of neurons showed degenerative changes, the morphology of oligodendrocytesshowed pre-apoptotic state, and the structure of myelin sheath layer collapsed. The number of synapses in thehippocampal CA1 area of mice in each drug intervention group was increased compared with the model group ( P <0. 01); the morphological structure of neurons and oligodendrocytes was relatively complete, the morphologicalstructure of neurons and oligodendrocytes was intact, the chromatin was uniform, and the myelin lamellar structure wasimproved. Luxol fast blue staining revealed that myelin fibers in the model group were significantly decreased and thestaining was lighter than that in the control group. The myelin fibers in the intervention groups were increased andstaining was deepened to different degrees. Conclusions Shenzheling oral liquid may play an early neuroprotectiverole in Alzheimer’s disease by increasing the number of synapses in the hippocampal CA1 area of App / Ps1 transgenic mice and improving the structure and morphology of myelin sheath, oligodendrocytes and neurons.
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