二苯乙烯苷对A53Tα-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  

Effects of tetrahydroxy-stilbene glucoside on motor function and dopaminergic neurons in substantia nigra of A53T α-synuclein transgenic mice

作　　者：张旭[1] 张如意[1] 陈晨[1] 张丽[1] 张兰[1] 李林[1] 

机构地区：[1]首都医科大学宣武医院药物研究室 北京市神经药物工程技术研究中心 神经变性病教育部重点实验室,100053

出　　处：《神经疾病与精神卫生》2017年第3期163-166,F0003,共5页Journal of Neuroscience and Mental Health

基　　金：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）

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A53Tα-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A53Tα-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.Objective To investigate the effects of tetrahydroxy-stilbene glucoside （TSG） on the behavioral and pathological changes in A53T mutantα-synuclein （α-syn） transgenic mice.Methods Six months old A53Tα-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 control group （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 A53Tα-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 ofα-syn transgenic mice.Conclusions TSG could obviously improve the motor function and increase the number of dopaminergic neurons in substantia nigra of A53Tα-syn mice. It is suggested that TSG may be beneficial to the treatment of synuclein-related neurodegenerative diseases such as Parkinson disease.

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 

分 类 号：R742.5[医药卫生—神经病学与精神病学]