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浙江大学学报（医学版） 2018年第5期47卷 480-486页

作者：吴忧梁顺利徐彬张荣博徐林胜浙江中医药大学附属第二医院神经内科浙江杭州310005

目的:观察姜黄素对帕金森病细胞模型中多巴胺能神经元的保护作用并探讨其作用机制。方法:人神经母细胞瘤SH-SY5Y细胞采用1-甲基-4-苯基-四氢吡啶离子(MPTP)处理建立帕金森病细胞模型,进一步设立姜黄素干预、自噬抑制剂3-甲基腺嘌呤(3-MA... 详细信息

目的:观察姜黄素对帕金森病细胞模型中多巴胺能神经元的保护作用并探讨其作用机制。方法:人神经母细胞瘤SH-SY5Y细胞采用1-甲基-4-苯基-四氢吡啶离子(MPTP)处理建立帕金森病细胞模型,进一步设立姜黄素干预、自噬抑制剂3-甲基腺嘌呤(3-MA)干预以及姜黄素和3-MA同时干预组。各组细胞在药物处理48 h后分别进行酪氨酸羟化酶(TH)免疫荧光染色观察多巴胺能神经元存活数;蛋白质印迹法检测α-突触核蛋白(α-Syn)、转录因子EB(TFEB)、自噬相关蛋白多克隆抗溶酶体相关膜蛋白2A(LAMP2A)和微管相关蛋白1轻链3-Ⅱ(LC3-Ⅱ)的蛋白表达; RT-PCR检测α-Syn的mRNA表达。结果:与模型对照组比较,姜黄素组多巴胺能神经元存活数增加(P<0.01),α-Syn蛋白及mRNA表达减少(均P<0.01),TFEB以及自噬蛋白LAMP2A和LC3-Ⅱ表达上调(均P<0.01);3-MA和姜黄素同时干预组多巴胺能神经元存活数增加(P<0.05),α-Syn蛋白及mRNA表达减少(P<0.05或P<0.01),TFEB、LAMP2A和LC3-Ⅱ蛋白表达上调(均P<0.01)。与姜黄素组比较,姜黄素和3-MA同时干预组多巴胺能神经元存活数减少,LC3-Ⅱ和LAMP2A蛋白表达减少(均P<0.05)。结论:姜黄素可激活细胞自噬功能促进α-Syn自噬性清除,从而减轻MPTP所致的多巴胺能神经元损伤。

关键词：姜黄素/药理学帕金森病/病理生理学神经元/代谢 α突触核蛋白转录因子自噬疾病模型, 动物

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Analysis of brain-stem auditory evoked potential and visual evoked potential in patients with Parkinson disease

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Neural Regeneration Research 2006年第5期1卷 449-452页

作者： Qiaorong Deng Jianzhong Deng Yanmin Zhao Xiaohai Yan Pin Chen Department of Anesthesiology Henan Provincial Tumor Hospital Zhengzhou 450008 Henan Province China Department of Neurology Anyang District Hospital Anyang 455000 Henan Province. China

BACKGROUND： With the development of neuroelectrophysiology, it had been identified that all kinds of evoked potentials might reflect the functional status of corresponding pathway. Evoked potentials recruited in the research of PD, it can be known whether other functional pathway of nervous system is impaired. OBJECTIVE： To observe whether brainstem auditory and visual passageway are impaired in patients with Parkinson disease （PD）, and compare with non-PD patients concurrently. DESIGN ： A non-randomized concurrent controlled observation. SETTINGS： Henan Provincial Tumor Hospital; Anyang District Hospital. PARTICIPANTS： Thirty-two cases of PD outpatients and inpatients, who registered in the Department of Neurology, Anyang District Hospital from October 1997 to February 2006, were enrolled as the PD group, including 20 males and 12 females, aged 50-72 years old. Inclusive criteria： In accordance with the diagnostic criteria of PD recommended by the dyskinesia and PD group of neurology branch of Chinese Medical Association. Patients with diseases that could cause Parkinson syndrome were excluded by CT scanning or MRI examination. Meanwhile, 30 cases with non-neurological disease were selected from the Department of Internal Medicine of our hospital as the control group, including 19 males and 11 females, aged 45-70 years old. Including criteria： Without history of neurological disease or psychiatric disease; showing normal image on CT. And PD, Parkinson syndrome and Parkinsonism-plus were excluded by professional neurologist. All the patients were informed and agreed with the examination and clinical observation. METHODS： The electrophysiological examination and clinical observation of the PD patients and controls were conducted. The Reporter type 4-channel evoked potential machine （Italy） was used to check brain-stem auditory evoked potential （BAEP） and visual evoked potential （VEP）. Why to be examined was explained to test taker. BAEP recording electrode wa

关键词：帕金森病/病理生理学帕金森病/病理学诱发电位听觉脑干老年人人类

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蝎毒对C57BL/6帕金森病小鼠脑内前脑啡肽原表达的影响

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中国临床康复 2006年第19期10卷 33-36页

作者：肖昭扬殷盛明于德钦高溪赵杰张万琴大连医科大学附属第一医院麻醉科辽宁省大连市116011 大连医科大学生理学教研室辽宁省大连市116027

目的:观察蝎毒对C57BL/6帕金森病小鼠运动协调与空间学习记忆能力以及脑内前脑啡肽原表达的影响。方法:实验于2004-03/06在大连医科大学生理学教研室进行。将96只C57BL/6小鼠随机分为模型组、模型给药组、单独给药组、盐水对照组,每组2... 详细信息

目的:观察蝎毒对C57BL/6帕金森病小鼠运动协调与空间学习记忆能力以及脑内前脑啡肽原表达的影响。方法:实验于2004-03/06在大连医科大学生理学教研室进行。将96只C57BL/6小鼠随机分为模型组、模型给药组、单独给药组、盐水对照组,每组24只。模型组为连续8d皮下注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(20mg/kg);模型给药和单独给药组给予蝎毒耐热蛋白连续8d,盐水对照组给等量生理盐水。测定爬杆、游泳实验评价运动协调能力。Morris水迷宫实验观察空间学习记忆能力。免疫细胞化学观察脑内多巴胺能神经元数目,反转录-聚合酶链反应测试脑内前脑啡肽mRNA改变。结果:96只小鼠均进入结果分析。①模型组小鼠的爬竿时间较盐水对照组、单独给药组延长,因此测试分数降低,出现运动障碍。模型给药组与模型组相比运动协调性障碍明显减轻(P<0.01)。模型组小鼠的游泳实验测试分数较盐水对照组降低,游泳能力降低,出现运动障碍。模型给药组与模型组相比运动障碍明显减轻(P<0.01)。②模型组小鼠寻找隐匿平台潜伏期明显比盐水对照组延长,盐水对照组小鼠空间学习能力下降。治疗组与模型组相比寻找隐匿平台潜伏期明显变短(P<0.01)。模型组小鼠于第5天在目标象限游泳时间占总时间百分比明显比盐水对照组降低,在对侧象限游泳时间占总时间百分比明显比盐水对照组增高(P<0.01)。模型组小鼠空间记忆能力下降。模型给药组与模型组相比有明显的改善(P<0.01)。③与盐水对照组相比,模型组小鼠黑质致密部的TH免疫反应阳性多巴胺能神经元明显脱失。模型给药组与模型组相比TH免疫反应阳性多巴胺能神经元数目明显增加(P<0.01)。④与盐水对照组相比,模型组小鼠脑区前脑啡肽原mRNA表达明显增强(P<0.05)。模型给药组与模型组相比前脑啡肽原mRNA表达明显降低(P<0.05)。结论:蝎毒保护中脑黑质致密部多巴胺能神经元并改善1-甲基-4-苯基-1,2,3,6-四氢吡啶引起的运动协调性降低和空间学习记忆障碍,其保护机制可能与降低异常的前脑啡肽原表达有关。

关键词：帕金森病/病理生理学空间行为记忆脑啡肽类/分泌

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揭示帕金森病患者运动迟缓的相关因素

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中国临床康复 2005年第21期9卷 170-173页

作者：王铭维顾平河北医科大学第一医院神经内科河北省石家庄市050031

目的:运动迟缓是造成帕金森病的主要特征,而肌无力、强直、震颤、运动多变、思维缓慢是其主要影响因素,而产生这些现象的机制是非常复杂的。资料来源:应用计算机检索“Medline”1980-01/2004-04的关于帕金森病运动迟缓的病理生理学机制... 详细信息

目的:运动迟缓是造成帕金森病的主要特征,而肌无力、强直、震颤、运动多变、思维缓慢是其主要影响因素,而产生这些现象的机制是非常复杂的。资料来源:应用计算机检索“Medline”1980-01/2004-04的关于帕金森病运动迟缓的病理生理学机制的文章,检索词“Parkinsondisease,bradyki-nesia,pathophysiology”,限定文章语言种类为“English”。资料选择:对资料进行初审,选取旨在探讨帕金森病运动迟缓相关影响因素的随机对照试验的文献,对选取的文献进行查找全文,排除重复研究。资料提炼:共选取36篇探讨帕金森病运动迟缓的相关文献,其中32篇文献与之相关,排除4篇重复研究。资料综合:总结所选文献中关于帕金森病运动迟缓的发病机制的内容,按照影响运动迟缓因素等几方面进行归类分析。其中6篇文献分析了运动迟缓的5种因素,15篇文献对帕金森病的发病机制及其他疾病做了比较,7篇文献对动物模型及手术机制做了探讨,支持手术可以改善帕金森病患者的运动功能。结论:运动迟缓的主要缺陷是运动减慢,在运动起始时肌力的反射强度不足,结果运动时偏离了所要达到的目的,而要采用多个小步来达到,由于在主动运动时运动命令设定的阈值低下而引起。

关键词：帕金森病/病理生理学运动障碍综述文献

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A dynamical-systems model for Parkinson's disease

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BIOLOGICAL CYBERNETICS 2000年第1期83卷 47-59页

作者： Connolly, CI Burns, JB Jog, MS SRI Int Ctr Artificial Intelligence Menlo Park CA 94025 USA Univ Western Ontario London Hlth Sci Ctr Movement Disorders Clin London ON N6A 5A5 Canada

The juxtaposition of hypokinetic and hyperkinetic symptoms in Parkinson's disease (PD) presents a challenge in modeling the basal ganglia. We propose a model of the striatum that can account for the mixture of symptoms seen in PD. In the model, the problem of motor planning is cast in terms of a particle in a potential, where potentials are generated internally in striatal modules, subject to afferent control. Planned movement is governed by Hamilton's equations, where potential energy is supplied by potentials expressed in the striatum. To test the model in realistic situations, a dynamic simulation of a two-link robot arm was used. Normal movement is modeled and shown to exhibit observed experimental properties. Symptoms of PD are reproduced by modeling hypothetical consequences of PD pathology.

关键词：抗震颤麻痹药/治疗应用步态/生理学运动机能减退/病理生理学左旋多巴/治疗应用模型神经学运动(Movement)/生理学帕金森病/药物疗法帕金森病/病理生理学体位/生理学人类

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Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease

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SCIENCE 2000年第5492期290卷 767-773页

作者： Kordower, JH Emborg, ME Bloch, J Ma, SY Chu, YP Leventhal, L McBride, J Chen, EY Palfi, S Roitberg, BZ Brown, WD Holden, JE Pyzalski, R Taylor, MD Carvey, P Ling, ZD Trono, D Hantraye, P Déglon, N Aebischer, P Rush Presbyterian St Lukes Med Ctr Dept Neurol Sci Chicago IL 60612 USA Rush Presbyterian St Lukes Med Ctr Dept Pharmacol Chicago IL 60612 USA Univ Lausanne Sch Med Div Surg Res Lausanne Switzerland Univ Lausanne Sch Med Gene Therapy Ctr Lausanne Switzerland Univ Wisconsin Dept Med Phys Madison WI 53706 USA Univ Wisconsin Dept Radiol Madison WI 53706 USA Univ Geneva Fac Med Dept Genet & Microbiol Geneva Switzerland Serv Hosp Frederic Joliot CEA Dept Rech Med Direct Rech MedCNRSUnite Rech Associe 2210 Orsay France Ecole Polytech Fed Lausanne Swiss Fed Inst Technol CH-1015 Lausanne Switzerland

Lentiviral delivery of glial cell Line-derived neurotrophic factor (Lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models of Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra of nonlesioned aged rhesus monkeys or young adult rhesus monkeys treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression with anterograde and retrograde transport was seen in all animals. In aged monkeys, Lenti-GDNF augmented dopaminergic function. In MPTP-treated monkeys, lenti-GDNF reversed functional deficits and completely prevented nigrostriatal degeneration. Additionally, Lenti-GDNF injections to intact rhesus monkeys revealed Long-term gene expression (8 months). In MPTP-treated monkeys, lenti-GDNF treatment reversed motor deficits in a hand-reach task. These data indicate that GDNF delivery using a Lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients.

关键词： 1-甲基-4-苯基-1 2 3 6-四氢吡啶衰老抗原 CD/分析二羟苯丙氨酸/类似物和衍生物二羟苯丙氨酸/代谢疾病模型动物多巴胺/代谢基因表达遗传载体胶质细胞源性神经营养因子慢病毒属/遗传学猕猴新纹状体/代谢新纹状体/病理学神经变性/预防和控制神经生长因子类神经组织蛋白质类/遗传学神经组织蛋白质类/代谢神经组织蛋白质类/治疗应用神经元/酶学帕金森病/代谢帕金森病/病理学帕金森病/病理生理学帕金森病/治疗帕金森障碍/代谢帕金森障碍/病理学帕金森障碍/病理生理学帕金森障碍/治疗精神运动性行为黑质/代谢黑质/病理学酪氨酸单氧化酶/代谢动物女(雌)性

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Cortical drives to human muscle: the Piper and related rhythms

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PROGRESS IN NEUROBIOLOGY 2000年第1期60卷 97-108页

作者： Brown, P Inst Neurol MRC Human Movement & Balance Unit London WC1N 3BG England UCL Natl Hosp Neurol & Neurosurg London WC1N 3BG England

During voluntary activity in humans, motor units are exposed to a number of descending drives that tend to synchronise motor unit activity at particular frequencies. In particular. the contralateral motor cortex drives muscle discharge in the beta (15-30 Hz) and Piper (30-60 Hz) bands. The cortical activity in these bands is task-specific, somatopicly distributed and generally precedes muscle discharge by an interval appropriate for conduction in fast pyramidal pathways. Coherence between cortex and muscle in the beta band is found during isometric contractions of weak to moderate strength. Thus oscillations within the beta band seem to coincide with a stable, relatively immutable state - a free running mode of the motor cortex that may maintain stable motor output with a minimum of computational effort. In contrast, coherence between cortex and muscle in the Piper band is most evident during strong isometric contractions or during movement. Demands on the motor cortex are likely to be greater and more mutable under these circumstances. Synchronisation in the gamma band may provide a means of binding together those particular, often spatially distributed, cortical elements involved in movement execution under conditions that vary from moment to moment and require some attention. Mechanisms both intrinsic and extrinsic to the cortex determine the pattern of rhythmic cortical activity. The basal granglia have a pivotal role in this regard, and inadequate output from these nuclei leads to a disappearance of the beta and Piper drives to muscle. This may in turn contribute to slowness and weakness in Parkinson's disease. (C) 1999 Elsevier Science Ltd. All rights reserved.

关键词：脑电描记术肌电描记术脑磁图描记术运动皮质/生理学肌骨骼/生理学肌阵挛/病理生理学帕金森病/病理生理学周期性动物人类

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An automated form of video image analysis applied to classification of movement disorders

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DISABILITY AND REHABILITATION 2000年第1-2期22卷 97-108页

作者： Chang, R Guan, L Burne, JA Univ Sydney Dept Elect Engn Sydney NSW 2006 Australia Univ Sydney Dept Biomed Sci Lidcombe NSW 2141 Australia

Video image analysis is able to provide quantitative data on postural and movement abnormalities and thus has an important application in neurological diagnosis and management. The conventional techniques require patients to be videotaped while wearing markers in a highly structured laboratory environment. This restricts the utility of video in routine clinical practise. We have begun development of intelligent software which aims to provide a more flexible system able to quantify human posture and movement directly from whole-body images without markers and in an unstructured environment. The steps involved are to extract complete human profiles from video frames, to fit skeletal frameworks to the profiles and derive joint angles and swing. distances. By this means a given posture is reduced to a set df basic parameters that can provide input to a neural network classifier. To test the system's performance we videotaped patients with dopa-responsive Parkinsonism and age-matched normals during several gait cycles, to yield 61 patient and 49 normal postures. These postures were reduced to their basic parameters and fed to the neural network classifier in various combinations. The optimal parameter sets (consisting of both swing distances and joint angles) yielded successful classification of normals and patients with an accuracy above 90 %. This result demonstrated the feasibility of the approach. The technique has the potential to guide clinicians on the relative sensitivity of specific postural/gait features in diagnosis. Future studies will aim to improve the robustness of the system in providing accurate parameter estimates from subjects wearing a range of clothing, and to further improve discrimination by incorporating more stages of the gait cycle into the analysis.

关键词：算法步态图像处理计算机辅助运动障碍/诊断运动障碍/康复神经网络(计算机) 帕金森病/病理生理学体位录像磁带人类

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Dimensionality of parkinsonian signs in aging and Alzheimer's disease

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JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES 1999年第4期54卷 M191-M196页

作者： Bennett, DA Shannon, KM Beckett, LA Wilson, RS Rush Alzheimers Dis Ctr Chicago IL 60612 USA Rush Inst Healthy Aging Chicago IL USA Rush Univ Dept Neurol Sci Chicago IL 60612 USA Rush Presbyterian St Lukes Med Ctr Chicago IL 60612 USA

Background. Parkinsonian signs are commonly found on the neurologic examination of older persons and are associated with morbidity and mortality. The extent to which parkinsonian signs in aging and Alzheimer's disease cluster in groups typical of Parkinson's disease has not been investigated previously. Methods. The motor portion of the Unified Parkinson's Disease Rating Scale (UPDRS), or a version with minor modifications, was administered to more than 2,800 persons in three cohorts: (a) 637 older persons with a wide range of neurologic conditions participating in the Chicago Health and Aging Project, a study of common health problems of a random sample of older persons from a geographically defined biracial community population;(b) 638 relatively healthy and highly educated older persons from 25 Catholic religious communities participating in the Religious Orders Study, a longitudinal clinical-pathologic study of aging;and (c) 1,546 older persons undergoing evaluation for possible dementia at the Push Alzheimer's Disease Center, an urban, tertiary care center that evaluates persons for possible dementia. Separate factor analyses were performed on each data set. Additional analyses examined the factor structure in subsets by gender and race, Results. A similar grouping of items emerged in each cohort and did not differ substantially by gender or race. The factors corresponded closely with the traditional grouping of parkinsonian signs into bradykinesia, gait disturbance, rigidity, and tremor. Conclusions. The grouping of parkinsonian si,ans is consistent in diverse samples of older persons and does not vary substantially across gender or race. The results provide an empirical basis for summarizing the principal motoric manifestations of parkinsonism.

关键词：非洲大陆世系人群衰老/生理学阿尔茨海默病/病理生理学队列研究痴呆/病理生理学欧洲大陆世系人群因素分析统计学步态/生理学纵向研究运动技能/生理学运动障碍/病理生理学肌僵硬/病理生理学肌骨骼/病理生理学神经病学检查帕金森病/病理生理学性别因素震颤/病理生理学老年人老年人 80以上女(雌)性人类男(雄)性

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Impact of sustained deprenyl (selegiline) in levodopa-treated Parkinson's disease: A randomized placebo-controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trial

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ANNALS OF NEUROLOGY 2002年第5期51卷 604-612页

作者： Shoulson, I Oakes, D Fahn, S Lang, A Langston, JW LeWitt, P Olanow, CW Penney, JB Tanner, C Kieburtz, K Rudolph, A Univ Rochester Med Ctr Rochester NY 14620 USA Columbia Presbyterian Med Ctr New York NY 10032 USA Toronto Western Hosp Toronto ON M5T 2S8 Canada Parkinsons Inst Sunnyvale CA USA Sinai Hosp Detroit MI 48235 USA Mt Sinai Sch Med New York NY USA

Deprenyl (selegiline) delays the need for levodopa therapy in patients with early Parkinson's disease, but the long-term benefits of this treatment remain unclear. During 1987 to 1988, 800 patients with early Parkinson's disease were randomized in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial to receive deprenyl, tocopherol, combined treatments, or a placebo and were then placed on active deprenyl (10mg/day). A second, independent randomization was carried out in early 1993 for 368 subjects who by that time had required levodopa and who had consented to continuing the deprenyl treatment (D subjects) or changing to a matching placebo (P subjects) under double-blind conditions. The first development of wearing off, dyskinesias, or on-off motor fluctuations was the prespecified primary outcome measure. During the average 2-year follow-up, there were no differences between the treatment groups with respect to the primary outcome measure (hazard ratio, 0.87;95% confidence interval, 0.63, 1.19;P = 0.38), withdrawal from the study, death, or adverse events. Although 34% of D subjects developed dyskinesias and only 19% of P subjects did (p = 0.006), only 16% of D subjects developed freezing of gait but 29% of P subjects did (P = 0.0003). Decline in motor performance was less in D subjects than P subjects. Levodopa-treated Parkinson's disease patients who had been treated with deprenyl for up to 7 years, compared with patients who were changed to a placebo after about 5 years, experienced slower motor decline and were more likely to develop dyskinesias but less likely to develop freezing of gait.

关键词：抗氧化剂/投药和剂量抗震颤麻痹药/投药和剂量卡方分布置信区间双盲法随访研究左旋多巴/治疗应用帕金森病/药物疗法帕金森病/病理生理学司立吉林/投药和剂量生育酚类/治疗应用治疗结果老年人女(雌)性人类男(雄)性中年人

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