茶多酚对帕金森病猴多巴胺能神经元保护作用的研究

doi:10.3969/j.issn.1006-7795.2015.05.005

首都医科大学学报 ›› 2015, Vol. 36 ›› Issue (5): 689-693.doi: 10.3969/j.issn.1006-7795.2015.05.005

• PD的发病机制与治疗 • 上一篇下一篇

茶多酚对帕金森病猴多巴胺能神经元保护作用的研究

陈宏伟¹, 于兰^2,3, 陈敏^2,3, 李旭冉^2,4, 李昕^2,4, 杨巍巍^2,4, 王鹏^2,4, 于顺^2,4,5

1. 朝阳区十八里店社区卫生服务中心, 北京 100122;
2. 首都医科大学宣武医院神经生物学研究室, 北京 100053;
3. 桂林医学院解剖学教研室, 桂林 541004;
4. 帕金森病研究北京重点实验室, 北京 100053;
5. 北京脑重大疾病研究院帕金森病研究所, 北京 100053

收稿日期:2015-09-14 出版日期:2015-10-21 发布日期:2015-10-20
基金资助:
国家重点基础研究发展计划(2011CB504101),国家自然科学基金(81071014, 81371200, 81401042),国家科技支撑计划课题(2012BAI10B03),北京市自然科学基金(7122035)),首都卫生发展科研专项课题(2011-4001-01)。

Protective effect of tea polyphenols on dopaminergic neuron in Parkinsonism disease monkeys

Chen Hongwei¹, Yu Lan^2,3, Chen Min^2,3, Li Xuran^2,4, Li Xin^2,4, Yang Weiwei^2,4, Wang Peng^2,4, Yu Shun^2,4,5

1. Chaoyang District Shibalidian Community Health Service Centers, Beijing 100122, China;
2. Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;
3. Department of Human Anatomy, Guilin Medical University, Guilin 541004, China;
4. Key Laboratory of Neurodegenerative Disease, Ministry of Education, Beijing 100053, China;
5. Center for Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China;

Received:2015-09-14 Online:2015-10-21 Published:2015-10-20
Contact: 于顺 E-mail:yushun103@163.com
Supported by:
This study was supported by Major State Basic Research Program (973 Program) of China (2011CB504101), National Natural Science Foundation of China (81071014, 81371200, 81401042), National Science and Technology Support Program (2012BAI10B03), Natural Science Foundation of Beijing (7122035), Capital Health Research and Development Special Fund (2011-4001-01).

摘要/Abstract

摘要： 目的探索茶多酚对1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP)诱导的帕金森病猴神经元的保护作用及机制。方法健康雌性食蟹猴年龄10~12岁,采用数字表法随机分为4组:正常对照组、茶多酚对照组(TP组)、帕金森病模型组(MPTP组)和茶多酚治疗组(MPTP + TP组),每组4只。正常对照组不进行任何处理;茶多酚对照组灌胃给予茶多酚80 d;PD模型组静脉注射MPTP诱导PD模型,茶多酚治疗组在PD模型建立后给予茶多酚治疗80 d,每周2次用帕金森病临床行为评价量表评价各组动物运动损伤。实验动物经安乐死后,分离脑组织,高效液相色谱分析纹状体多巴胺及其代谢产物含量,免疫组织化学和体视学分析黑质多巴胺能神经元变化。结果 TP能减少MPTP诱导的食蟹猴黑质多巴胺能神经元的损伤并缓解其运动障碍。结果首次在灵长类动物体内实验证实茶多酚能有效减少多巴胺能神经元的损伤并改善其运动机能。

关键词: 茶多酚, 运动障碍, 多巴胺能神经元, 帕金森病

Abstract: Objective To investigate the protecting efficacy of tea polyphenols on dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinson's disease monkeys and its mechanism. Methods Healthy female cynomolgus monkeys 10 to 12 years old were randomly divided into four groups: normal control group (n= 4), TP group (n=4), MPTP group (n=4), and MPTP + TP group (n=4). Control group were not given any treatment; The TP group monkeys were treated with TP by gastrogavage once daily for 80 consecutive days. In MPTP and MPTP+TP groups, MPTP was injected intravenously as MPTP-HCl to induce PD model. The MPTP+TP groups were treated with TP by gastrogavage once daily for 80 consecutive days after making PD model. Motor deficits were quantified twice a week by a previously validated Parkinsonian monkey clinical rating scale. All animals were euthanized and the brains tissues were rapidly separated. To measure the levels of dopamine and its metabolites in the striatum were measured using HPLC method. Dopaminergic neurons were identified by immunohistochemistry and stereology. Results Tea polyphenols alleviated MPTP-induced injury of nigral dopaminergic neurons and improved motor impairments in cynomolgus monkeys (P<0.05). Conclusion This study showed first in vivo evidence that TP could alleviate dopaminergic neuronal injury and motor impairments in nonhuman primates.

Key words: tea polyphenols, motor impairments, dopaminergic neuronal, Parkinson's disease

中图分类号:

R338

陈宏伟, 于兰, 陈敏, 李旭冉, 李昕, 杨巍巍, 王鹏, 于顺. 茶多酚对帕金森病猴多巴胺能神经元保护作用的研究[J]. 首都医科大学学报, 2015, 36(5): 689-693.

Chen Hongwei, Yu Lan, Chen Min, Li Xuran, Li Xin, Yang Weiwei, Wang Peng, Yu Shun. Protective effect of tea polyphenols on dopaminergic neuron in Parkinsonism disease monkeys[J]. Journal of Capital Medical University, 2015, 36(5): 689-693.

参考文献

[1] SamⅡ A, Nutt J G, Ransom B R. Parkinson's disease [J]. Lancet, 2004, 363 (9423): 1783-1793.
[2] Wales P, Pinho R, Lazaro D F, et al. Limelight on alpha-synuclein: pathological and mechanistic implications in neurodegeneration [J]. J Parkinsons Dis, 2013, 3 (4): 415-459.
[3] Jethva P N, Kardani J R, Roy I. Modulation of alpha-synuclein aggregation by dopamine in the presence of MPTP and its metabolite [J]. FEBS J, 2011, 278 (10): 1688-1698.
[4] Yu S, Li X, Liu G, et al. Extensive nuclear localization of alpha-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody [J]. Neuroscience, 2007, 145 (2): 539-555.
[5] Kurlan R, Kim M H, Gash D M. The time course and magnitude of spontaneous recovery of parkinsonism produced by intracarotid administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to monkeys [J]. Ann Neurol, 1991, 29 (6): 677-679.
[6] Lane T A, Boerner T, Bannerman D M, et al. Decreased striatal dopamine in group Ⅱ metabotropic glutamate receptor (mGlu2/mGlu3) double knockout mice [J]. BMC Neurosci, 2013, 14: 102.
[7] Mackey S, Jing Y, Flores J, et al. Direct intranigral administration of an ubiquitin proteasome system inhibitor in rat: behavior, positron emission tomography, immunohistochemistry [J]. Exp Neurol, 2013, 247: 19-24.
[8] Beal M F. Experimental models of Parkinson's disease [J]. Nat Rev Neurosci, 2001, 2 (5): 325-334.
[9] Kozina E A, Khakimova G R, Khaindrava V G, et al. Tyrosine hydroxylase expression and activity in nigrostriatal dopaminergic neurons of MPTP-treated mice at the presymptomatic and symptomatic stages of parkinsonism [J]. J Neurol Sci, 2014, 340 (1-2): 198-207.
[10] Hare D J, Adlard P A, Doble P A, et al. Metallobiology of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity [J]. Metallomics, 2013, 5 (2): 91-109.
[11] Kim H S, Quon M J, Kim J A. New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate[J]. Redox Biol, 2014, 2: 187-195.
[12] 尹娜, 陈予东,李昕,等. 帕金森病患者血浆增强-突触核蛋白寡聚体形成[J]. 首都医科大学学报,2013,34(6) :840-843.
[13] 王鹏, 李昕,陈予东,等. α-突触核蛋白寡聚体抑制大鼠原代培养神经元突起早期生长[J]. 首都医科大学学报,2014,35(5):587-591.

[1]	粟文婷, 於佳楠, 贾军, 王晓民. 电针对帕金森病模型小鼠纹状体背侧的c-Fos表达的选择性调节[J]. 首都医科大学学报, 2021, 42(6): 986-992.
[2]	高歌, 查旭, 刘伟进, 杨慧. 129位丝氨酸磷酸化α-突触核蛋白DELFIA检测方法的建立及初步应用[J]. 首都医科大学学报, 2021, 42(5): 776-782.
[3]	王梦月, 赵鑫, 曹枭, 王可, 贾军. 帕金森病小鼠模型自主活动状态下的运动启动分析[J]. 首都医科大学学报, 2021, 42(4): 553-558.
[4]	袁惠莉, 宫晓丽, 范征, 梁志刚, 王晓民. 远志皂苷对脂多糖诱导的帕金森病模型大鼠的作用及机制研究[J]. 首都医科大学学报, 2020, 41(6): 914-922.
[5]	宋启晗, 李旭冉, 李昕, 杨巍巍, 李伟, 于顺. 不同亚型的帕金森病及多系统萎缩患者血浆α-突触核蛋白寡聚体浓度分析[J]. 首都医科大学学报, 2020, 41(2): 212-216.
[6]	丁晖, 蔡彦宁, 陈彪. 灵芝提取物对MPP⁺诱导的Neuro-2a细胞自噬的影响[J]. 首都医科大学学报, 2019, 40(4): 596-601.
[7]	张辉, 马惠清, 王森茂, 王晓娟. 银杏叶提取物对帕金森病模型大鼠脑内神经炎性反应的影响[J]. 首都医科大学学报, 2019, 40(3): 439-442.
[8]	李杰, 谢秀娟, 宋炜, 潘维花, 杨巍巍, 于顺. 帕金森病患者血浆增强α-突触核蛋白细胞毒性及其机制研究[J]. 首都医科大学学报, 2019, 40(2): 244-250.
[9]	刘梦茹, 宫晓丽, 王乐, 刘玚, 张婷, 王晓民. 脂多糖对肠道α-突触核蛋白表达的影响[J]. 首都医科大学学报, 2018, 39(4): 557-562.
[10]	罗斌斌, 胡亚松, 岳峰, 陈彪. MPTP诱导的食蟹猴偏侧帕金森病模型运动行为学的长期动态评价研究[J]. 首都医科大学学报, 2018, 39(2): 217-222.
[11]	卢勇泉, 陈敏, 高歌, 段春礼, 鲁玲玲, 杨慧. TRPC3参与α-突触核蛋白引起的线粒体损伤[J]. 首都医科大学学报, 2017, 38(6): 857-862.
[12]	刘俊华, 王勇, 王颜颜, 王晓民. 深部脑磁刺激对帕金森病模型大鼠运动症状治疗的安全性评价[J]. 首都医科大学学报, 2017, 38(2): 260-267.
[13]	王琳, 袁海宁, 贾竑晓, 朱虹, 康玉春. “白虎消迟汤”治疗迟发性运动障碍疗效总结[J]. 首都医科大学学报, 2016, 37(2): 219-222.
[14]	卢剑清, 邓玉林. S-腺苷甲硫氨酸增加salsolinol对多巴胺能神经细胞SH-SY5Y的毒性[J]. 首都医科大学学报, 2015, 36(6): 915-920.
[15]	张如意, 张丽, 李林. 线粒体功能障碍、α-突触核蛋白与帕金森病[J]. 首都医科大学学报, 2015, 36(6): 861-864.

茶多酚对帕金森病猴多巴胺能神经元保护作用的研究

Protective effect of tea polyphenols on dopaminergic neuron in Parkinsonism disease monkeys

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价