免疫机制与帕金森病关系的研究

目的　探讨免疫机制与帕金森病 (PD)发病的相关性。方法　采用PD患者的血清IgG建立PD的细胞模型 ,将纯化的PD患者、疾病对照组患者及正常人的血清IgG或 /及补体加入大鼠胚胎中脑神经元 胶质细胞混合培养体系中 ,通过MTT法检测细胞活力 ,免疫细胞化学法评价多巴胺 (DA)能细胞的数目、形态。结果　单独PDIgG(6 0 μg/ml)或补体对原代中脑神经元 胶质细胞混合培养体系中的DA能神经元的数目、形态无明显影响 (P >0 0 5 ) ;当培养体系同时接受二者处理时 ,抗酪氨酸羟化酶 (TH)阳性细胞数明显减少 (P <0 0 1) ,突起明显减少和缩短 ,β tubulin阳性细胞数和形态无明显变化 (P >0 0 5 ) ,总的细胞活力无明显下降(P >0 0 5 ) ,PDIgG(0、2 0、6 0、10 0 μg/ml)依赖补体对DA能神经元的毒性作用呈剂量依赖性。疾病对照组和正常对照组的血清IgG即使在补体存在时对TH阳性细胞数、形态也无明显影响 (P >0 0 5 )。结论　在补体存在时 ,用PDIgG可建立PD的细胞模型 ,提示PD的发病可能涉及免疫机制     

帕金森病与线粒体功能障碍

概述了帕金森病(PD)患者线粒体功能障碍的组织、异常的酶复合体及其原因,讨论了线粒体功能障碍在PD中的发病机制和监测PD患者周围组织中的线粒体酶复合体活性的临床意义。     

鱼藤酮的多巴胺神经元毒性与帕金森病

野生植物毛鱼藤液汁中含有六种鱼藤酮类化合物 ,其中鱼藤酮毒性最大。鱼藤酮能与线粒体复合物I(complexI)即NADH脱氢酶结合并抑制其活性 ,阻断细胞呼吸链的递氢功能和氧化磷酸化过程 ,从而产生细胞毒作用。近年研究发现 ,长期暴露于鱼藤酮的大鼠中脑DA神经元内出现典型的Lewy小体 ,Flouro -JadeB等多种方法等均证实其DA神经元的退行变性 ,而胆碱能神经系统未受影响。同时 ,鱼藤酮中毒大鼠还出现行动呆滞、僵住症等帕金森病样临床症状。这些结果提示鱼藤酮对中枢DA神经系统有选择性损伤作用。本文结合近年来对帕金森病研究的进展 ,从不同角度分析鱼藤酮与帕金森病的相关性。     

POLG基因与帕金森病关系的研究进展

帕金森病（Parkinson disease，PD）是继阿尔茨海默病（AD）之后的第二大类神经变性病，在欧美的发病率约为0．4％-2．2％。这一疾病的病理学改变为黑质的多巴胺能神经元的选择性进行性缺失。迄今为止，病因尚未明确。目前普遍认为是由遗传易患性和环境因素相互作用的结果。自从1986年Vyas等在1-甲基4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的PD小鼠模型中发现了线粒体氧化呼吸链酶复合物Ⅰ的活性下降及多巴胺能神经元的变性死亡后，人们就开始怀疑线粒体与PD的发病有关。     

帕金森病与炎症反应关系研究进展

帕金森病 (Parkinsondisease ,PD)的病因和引起多巴胺 (DA)能神经元变性的准确机制至今仍未充分阐明 ,近几年来 ,随着人们对PD研究的不断深入 ,发现炎症反应 (主要是指小胶质细胞的异常激活 )可能参与了PD的DA能神经元进行性变性进程 ,我们就有关PD炎性反应特点及其参与PD病理过程的最新研究进展介绍如下。一、PD患者脑内存在炎症反应证据近年来诸多学者报道 ,PD患者脑脊液和黑质纹状体系统中炎性细胞因子均较健康对照组增高。这些细胞因子包括致炎性细胞因子 :肿瘤坏死因子 α(TNF α)、白细胞介素 1β(IL 1β)、白细胞介素 1(…     

炎症反应在帕金森病中的研究进展

帕金森病(PD)是常见的中枢神经系统变性疾病,以黑质和纹状体多巴胺能神经元进行性缺失为主要病理改变,其病因和发病机制不明。近年来,炎症反应能够导致多巴胺能神经元变性、死亡的研究引起人们广泛关注。非甾体类药物的抗炎症反应作用可延缓PD的进展。炎症反应在PD中的作用研究已成为该领域新的研究热点。本文介绍炎症反应在PD中的作用以及研究进展。     

神经干细胞移植治疗帕金森病的研究进展

帕金森病(PD)是一种常见的中枢神经系统变性疾病，发病率约为1％，其病理特征主要是中脑黑质．纹状体通路多巴胺能神经元进行性变性，造成纹状体内多巴胺含量减少，当黑质纹状体多巴胺能神经元丢失70％时出现典型的临床症状。PD的最初药物治疗给许多患者带来了益处，但疗效是暂时的，因为左旋多巴并不能阻止多巴胺能神经元的进行性     

多巴胺受体基因多态性与帕金森病遗传易患性的关系

为了探讨多巴胺受体 (ＤＲ)基因多态性与帕金森病(ＰＤ)遗传易患性的关系 ,我们对一组ＰＤ患者和正常人的ＤＲＤ2、ＤＲＤ3、ＤＲＤ5基因多态性进行了病例 对照研究。1.研究对象 :140例原发性ＰＤ患者来自我院神经科ＰＤ门诊 ,均按照ＣＡＰＩＴ标准确诊。其中男性 85例 ,女性 5 5例 ,起病年龄 30～ 86岁 ,平均 (5 6 .8± 10 .8)岁 ,病程为 0 .5～ 2 2年。全部患者均应用左旋多巴类药物治疗 ,疗程为 0 .5～ 2 0年。选择与患者组年龄和性别基本匹配的 141名健康成年人作为对照组 ,其中男性 81名 ,女性 6 0名 ,年龄 2 8～ 83岁 ,平均 (5 5 .5…     

新型多巴胺受体激动剂与帕金森病

帕金森病(Parkinson's disease.PD)是一种常见的锥体外系疾病,临床表现以震颤、肌肉僵硬为主.伴有植物神经功能、认知和情感功能障碍等非运动症状Ⅲ.其病理改变为中脑黑质的多巴胺(dopamine.DA)能神经元缓慢进行性变性和死亡,导致黑质、纹状体DA转运体、DA显著减少.最终导致锥体外系功能失调,从而出现上述行为障碍.     

基因修饰的神经干细胞与帕金森病

神经干细胞具备自我更新能力,可在特定环境下定向分化为神经元和胶质细胞,通过分泌神经营养因子、调控神经炎症、增强神经元可塑性等机制修复帕金森病(PD)多巴胺神经元损伤。目前PD治疗主要是多巴胺替代治疗,但不能阻止PD病情进展,且不能彻底根治。干细胞在PD中具有较好的治疗前景,尤其神经干细胞优势引起较多关注。尽管神经干细胞移植在PD治疗中取得了一定的效果,但临床中的应用仍受到很多条件限制。本文就神经干细胞基因修饰在PD治疗中的研究进展进行综述,旨在探讨神经干细胞治疗PD的关键调控机制。     

血清胰岛素样生长因子-1与帕金森病关系的研究

帕金森病是中老年人群中最常见的神经系统退行性疾病之一,其主要病理特征是黑质致密部多巴胺能神经元的变性丢失,引起多巴胺分泌不足。胰岛素样生长因子-1能促进多巴胺能神经元的存活,且相关实验证实帕金森病患者血清胰岛素样生长因子-1水平发生了变化。文中对血清胰岛素样生长因子-1与帕金森病的关系作一综述。     

Skeletal Growth Acceleration with Growth Hormone Secretagogues in Transgenic Growth Retarded Rats: Pattern-Dependent Effects and Mechanisms of Desensitization

The transgenic growth retarded (Tgr) rat is the first genetic model of growth hormone (GH) deficiency whose growth can be accelerated with exogenous GH secretagogues (GHSs). In this study, we have demonstrated that GHS-receptor (GHS-R) mRNA expression in the arcuate nucleus of Tgr rats was not significantly different to that in wild-type littermates. We have confirmed that GHS-induced elevation in body weight gain was accompanied by acceleration of skeletal growth, and that the effects of the GHS, GHRP-6, were both dose- and pattern-dependent. The growth response with continuous infusion of GHRP-6 was transient, accompanied by suppression of GH and corticosterone responses to bolus injection of GHRP-6. This desensitization occurred without downregulation of arcuate GHS-R mRNA expression, but was accompanied by elevated periventricular somatostatin mRNA expression. In contrast, pulsatile (3-hourly) infusion of GHRP-6 produced sustained growth and GH responses, which were accompanied by suppression of corticosterone responses and elevated arcuate GH-releasing factor (GRF) mRNA expression. Skeletal growth was further accelerated by coinfusion of GRF, but significant depletion of pituitary GH stores suggested that this growth rate may not be sustainable. These experiments confirm the importance of the Tgr rat for investigating the growth promoting potential of the GHSs in the context of GH-deficient dwarfism, and suggest that elevated somatostatin expression may mediate the suppression of the GRF-GH and hypothalamo-pituitary-adrenal axes following continuous GHRP-6 treatment.     

帕金森病与细胞凋亡的新进展

帕金森病的病因和发病机理尚不十分清楚。最近的研究表明细胞凋亡可能在帕金森病的黑质多巴胺能神经元死亡中起重要作用，本综述了近年的研究进展。     

还原型谷胱甘肽对帕金森病保护性治疗的实验研究

目的观察还原型谷胱甘肽对帕金森病(PD)大鼠模型的保护性治疗作用,并探讨其作用机理.方法应用6-羟基多巴制作PD大鼠模型.将大鼠模型随机分为4组(每组8只):模型组,谷胱甘肽(GSH)组,左旋多巴(Ldopa)组,谷胱甘肽 左旋多巴组,另设对照组(8只),分别给予相应处理,共45天,给药前后均进行行为学测试,给药结束后行免疫组化和电镜观察,并测定黑质区谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、活性氧(ROS)及线粒体呼吸链酶复合体Ⅰ水平.结果 (1)GSH对其旋转行为无明显影响(P＞0.05);(2)GSH 能减轻黑质区氧化应激损伤;(3)GSH能增强黑质呼吸链酶复合体Ⅰ活性;(4)免疫组化发现GSH组TH-IR神经元较模型组明显增多(P＜0.001);(5)电镜下发现GSH可部分延缓凋亡进程.结论 (1)GSH能减轻黑质区氧化应激损伤,并对线粒体呼吸链具有一定保护作用;(2)GSH与L-dopa合用既可有效改善症状,又对残存黑质多巴胺能神经元具有保护性治疗作用.     

lntra- and Inter-Individual Variability in Growth Hormone Responses to Growth Hormone-Releasing Hormone*

Normal subjects show a wide range of growth hormone (GH) responses to growth hormone-releasing hormone (GHRH) stimulation, but it is uncertain whether this variability reflects differences among individuals or whether it would also be observed on repeated tests of the same subject. To clarify this, we tested nine normal men repeatedly with iv bolus doses of 1 μg/kg GHRH(1–44)NH₂. Most subjects showed wide variations in their GH responses on repeated testing, and the intra-individual variability was nearly as great as the inter-individual variability in responses, accounting for about two-thirds of the overall variance. A minority of subjects had lower and less variable responses. Ultradian fluctuations in hypothalamic somatostatin secretion may account for this marked intra-individual variability.     

左旋多巴在帕金森病治疗中的地位及进展

数十年来,左旋多巴曾为帕金森病(PD)治疗带来革命性的改变,并始终作为PD治疗的金标准享有及其重要的地位。然而,伴随其治疗产生的运动并发症却成为困扰医患的一大难题。近年来,随着对运动并发症机制的研究,越来越多的证据表明持续性多巴胺能刺激(CDS)可在产生良好疗效的同时降低运动并发症的风险,故其被作为PD治疗的新理念备受关注。为此,大量研究致力于开发能形成CDS状态的左旋多巴新制剂,从而探寻出提高疗效与降低运动并发症之间的平衡点。文中就左旋多巴治疗PD的回顾及进展予以介绍。     

F Response Abnormality in Parkinson's Disease

Abstract: The F response was recorded from the 1st dorsal interosseous muscle (1st DI) two antagonistic muscles, the flexor digitorurn brevis (FDB) the extensor digitorum brevis (EDB), in 16 patients with Parkinson's disease 22 age-matched normal controls. In Parkinson's disease, the F responses from the 1st DI the FDB occurred more frequently with a longer duration a greater number of phases in comparison with the normal controls. In addition, the coefficient of variation of onset latency was significantly smaller in Parkinson's disease. On the other hand, the F response recorded from the EDB showed the same tendency as that from the FDB, but not to a significant extent. These findings suggest that the excitability of the spinal motor neurons is enhanced in rigid parkinsoninn patients. It thus seems reasonable to assume that the main underlying cause of rigidity is an excessive supraspinal drive to the spinal motor neurons, including an increase in motoneuron excitability.     

Astrocyte reactivity in related brain regions in a mouse model of MPTP-induced Parkinson's disease

BACKGROUND: Severe injury to dopaminergic neuronal cell bodies and their axon terminals in the substantia nigra pars compacta (SNC) has been observed in both Parkinson's disease (PD) patients or in 1-methy-4-phenyl-1,2,3,6-tetrahydropyrindine(MPTP)-induced PD animal models, but only slight injury occurs in the adjacent ventral tegmental area (VTA). The mechanisms underlying this selective injury remain poorly understood.OBJECTIVE: To comparatively observe astrocyte reactivity in the SNC, caudate putamen (Cpu), VTA, and frontal association cortex (FrA).DESIGN, TIME AND SETTING: A cellular and molecular biology, randomized, controlled experiment was performed at the Institute of Neurobiology, Department of Human Anatomy, Medical School of Nantong University, between December 2006 and September 2008.MATERIALS: A total of 80 healthy adult male C57BL/6 mice were included in this study. MPTP was purchased from Sigma, USA.METHODS: Mice were randomly divided into a model group (n = 64) and a sham-operated group (n = 16). PD was induced in the mice from the model group by intraperitoneal injection of 20 mg/kg MPTP, once every three hours, for a total of 4 times.MAIN OUTCOME MEASURES: Tyrosine hydroxylase (TH)-immunoreactive neurons and glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes were examined by dual immunofluorescence labeling. GFAP-immunoreactive astrocytes in the Cpu and FrA were determined by immunofluorescent staining. GFAP mRNA expression in the SNC, Cpu, VTA, and FrA was detected using real-time polymerase chain reaction. TH protein levels in the TH-immunoreactive axon terminals of the Cpu and FrA were detected by Western blotting.RESULTS: Numbers of TH-immunoreactive neurons in the SNC, and TH protein level in the Cpu, markedly decreased (by approximately 68%) 1 day after MPTP injection, and gradually increased at 3 days. Simultaneously, astrocyte reactivity was strengthened, in particular at 7 days. However, after MPTP injection, decreases in the numbers of TH-immunoreactive neurons in the VTA, and TH protein levels in the FrA, were less apparent (approximately 15%). Also, no obvious astrocyte reactivity was observed.CONCLUSION: In a mouse model of PD, astrocyte reactivity was apparent in the SNC and Cpu, but not the VTA or FrA. In addition, astrocyte reactivity was greater in regions where injury to dopaminergic neurons was more severe.