二苯乙烯苷对PD模型小鼠干预作用的观察及机制初探

doi:10.3969/j.issn.1006-7795.2014.06.012

首都医科大学学报 ›› 2014, Vol. 35 ›› Issue (6): 735-740.doi: 10.3969/j.issn.1006-7795.2014.06.012

• 神经系统常见病的基础研究 • 上一篇下一篇

二苯乙烯苷对PD模型小鼠干预作用的观察及机制初探

张如意¹, 张丽¹, 吴燕川², 李林¹

1. 首都医科大学宣武医院药物研究室北京市老年病医疗研究中心神经变性病教育部重点实验室, 北京 100053;
2. 首都医科大学宣武医院中心实验室, 北京 100053

收稿日期:2014-08-18 发布日期:2014-12-15
通讯作者: 李林 E-mail:linli97@hotmail.com
基金资助:
国家自然科学基金(81273498),首都卫生发展科研专项基金(2011-1001-04)

Effects of tetrahydroxystilbene glucoside on behavior and dopaminergic neurons in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced model mice

Zhang Ruyi¹, Zhang Li¹, Wu Yanchuan², Li Lin¹

1. Department of Pharmacology, Xuanwu Hospital, Capital Medical University, Beijing Geriatric Medical Research Center, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China;
2. Department of Central Lab, Xuanwu Hospital, Capital Medical University, Beijing 100053, China

Received:2014-08-18 Published:2014-12-15
Supported by:
This study was supported by the National Natural Science Foundation of China(81273498), The Capital Health Research and Development Foundation(2011-1001-04).

摘要/Abstract

摘要：

目的观察二苯乙烯苷(tetrahydroxystilbene glucoside,TSG)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine,MPTP)拟帕金森病(Parkinson's disease,PD)模型小鼠行为学及多巴胺能神经元的影响。方法 C57BL小鼠按数字表法随机分为对照组、模型组、TSG小剂量组(TSG 60 mg/kg)和TSG大剂量组(TSG 120 mg/kg)。MPTP 30 mg/kg腹腔注射5 d建立拟PD小鼠模型。采用爬杆实验、转棒实验和自主活动实验测试小鼠行为学变化。免疫组织化学法检测各组小鼠黑质处酪氨酸羟化酶(tyrosine hydroxylase,TH)阳性细胞的表达情况。高效液相色谱电化学检测法测定小鼠纹状体内多巴胺及其代谢产物的含量。结果与对照组相比,MPTP模型组小鼠爬杆时间显著延长,在转棒上的停留时间明显缩短,自主活动数减少,脑黑质处TH阳性细胞数量显著减少,纹状体内多巴胺及其代谢产物含量显著降低。与模型组小鼠相比,TSG用药组小鼠运动协调性显著增强,脑黑质处TH阳性细胞数量增加,纹状体内多巴胺含量升高。结论 TSG可改善MPTP模型小鼠的行为学,保护黑质多巴胺能神经元。TSG可能具有潜在的防治PD的作用。

关键词: 二苯乙烯苷, 1-甲基-4-苯基-1,2,3,6-四氢吡啶, 帕金森病, 行为学, 多巴胺

Abstract:

Objective To observe effects of tetrahydroxystilbene glucoside(TSG) on behavior and content of dopamine and its metabolites in striatum of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP) model mice. Methods Mice were randomly divided into normal control group, model group, and TSG low dose(60 mg/kg) and high dose(120 mg/kg) groups. The behavior changes of mice were observed by pole test, Rotarod test and spontaneous movement test. The tyrosine hydroxylase(TH) positive cells were detected by immunohistochemical method. The content of dopamine(DA) and its metabolic products in striatum were determined by HPLC-ECD. Results MPTP model mice showed behavior deficit. The counts of TH positive neurons in substantia nigra and the content of dopamine and its metabolites in striatum in model mice decreased significantly compared with control group. TSG ameliorated the behavior deficits, increased the number of TH positive neurons in the substantia nigra, and elevated the content of dopamine in striatum compared with model mice. Conclusion TSG protected dopaminergic neurons against MPTP-induced damage, and may become a candidate drug for prevention and treatment of Parkinson's disease.

Key words: tetrahydroxystilbene glucoside, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, Parkinson's disease, behavior, eopamine

中图分类号:

R965.1

张如意, 张丽, 吴燕川, 李林. 二苯乙烯苷对PD模型小鼠干预作用的观察及机制初探[J]. 首都医科大学学报, 2014, 35(6): 735-740.

Zhang Ruyi, Zhang Li, Wu Yanchuan, Li Lin. Effects of tetrahydroxystilbene glucoside on behavior and dopaminergic neurons in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced model mice[J]. Journal of Capital Medical University, 2014, 35(6): 735-740.

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二苯乙烯苷对PD模型小鼠干预作用的观察及机制初探

Effects of tetrahydroxystilbene glucoside on behavior and dopaminergic neurons in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced model mice

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