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二苯乙烯苷对A53T α-突触核蛋白转基因小鼠运动功能和黑质多巴胺能神经元的影响
张旭张如意陈晨张丽张兰李林
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摘要:
目的 研究二苯乙烯苷(TSG) 对A53T 突变型α-突触核蛋白(α-syn) 转基因小鼠运动功能和病理变化的影响。方法 6 月龄A53T α-syn 转基因阳性小鼠分为模型组(Tg+)、模型+TSG 小剂量组(50 mg/kg) 、模型+TSG 大剂量(100 mg/kg) 组。同窝转基因阴性小鼠随机分为对照组(Tg-)、对照+TSG 大剂量组(100 mg/kg) 组。给药组每天灌胃给予TSG,共9 个月,至15 月龄;对照组和模型组每天灌胃给予等容积蒸馏水。应用爬杆试验和筑巢试验检测小鼠的运动能力;应用免疫组织化学方法检测小鼠黑质酪氨酸羟化酶(TH) 标记的神经元。结果 与转基因阴性的对照组小鼠比较,模型组小鼠在爬杆试验中的潜伏期延长,筑巢行为评分减低,黑质致密部的TH 阳性神经元数量减少。TSG 灌胃给药9 个月能够明显缩短模型小鼠在爬杆试验中的潜伏期,增高筑巢行为评分,增加黑质致密部TH 阳性细胞数量。结论 TSG 能够明显改善A53T α-syn 转基因小鼠的运动功能,增高黑质多巴胺能神经元数量,提示TSG 可能有利于治疗帕金森病等突触核蛋白相关疾病。
关键词:  帕金森病  α-突触核蛋白  小鼠,转基因  二苯乙烯苷  行为学  多巴胺能神经元
DOI:10.3969/j.issn.1009-6574.2017.03.003
基金项目:国家自然科学基金项目(81273498);国家重大新药创制科技重大专项(2015ZX09101016001);首都卫生发展科研专项(2016-2-1033);北京市教委新医药学科群项目(XK100270569);北京市高层次卫生技术人才项目(2011-1-7,2014-2-014)
Effects of tetrahydroxy-stilbene glucoside on motor function and dopaminergic neurons in substantia nigra of A53T α-synuclein transgenic mice
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Abstract:
bjective To investigate the effects of tetrahydroxy-stilbene glucoside (TSG) on thebehavioral and pathological changes in A53T mutant α-synuclein (α-syn) transgenic mice. Methods  Six months old A53T α-syn transgenic mice were divided into model group (Tg+ group),model+ low dose group(50 mg/kg) and model+high dose group (100 mg/kg). Brood negative transgenic mice were divided into controlgroup (Tg-) and high dose group (100 mg/kg). The administration groups were given TSG by gavage everyday for 9 months,while the control and model groups were given equal volume of distilled water. The movement abilities of mice were measured by pole test and nest building test. The immunohistochemical method was used to detect ty-rosine hydroxylase (TH)-labeled neurons in the substantia nigra of mice. Results Compared to negative trans-genic mice,the latency prolonged in pole test and the score of nest building were decreased,and the number of TH positive neurons were declined in substantia nigra compacta of A53T α-syn transgenic mice. Intragastrical administration of TSG for 9 months significantly shortened the latency in pole test,increased the score of nest building,and increased the number of TH positive neurons in substantia nigra compacta of α-syn transgenic mice. Conclusions  TSG could obviously improve the motor function and increase the number of dopaminergic neurons in substantia nigra of A53T α-syn mice. It is suggested that TSG may be beneficial to the treatment of synuclein-related neurodegenerative diseases such as Parkinson disease.
Key words:  Parkinson disease  Alpha-synuclein  Mice,transgenic  Tetrahydroxy-stilbene glu-coside  Behavior  Dopaminergic neuron

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