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丙戊酸钠对帕金森病模型小鼠多巴胺能神经元及脑源性神经营养因子表达的影响
帕金森病(Parkinson's disease,PD)是一种神经系统退行性疾病,主要表现为中脑黑质致密部多巴胺能神经元丧失,纹状体多巴胺含量下降,至今尚无有效的治疗手段.丙戊酸钠(Valproate, VPA)是临床上作为治疗双相精神障碍的主要药物.
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脑源性神经营养因子对血管新生的作用
脑源性神经营养因子 (brain-derived neurotrophic factor, BDNF) 是神经营养因子家族的一员,对中枢和外周神经系统多种类型神经元的生长、发育、分化和再生具有重要作用[1].研究显示人脐静脉内皮细胞(HUVEC)、人脑血管内皮细胞等多种内皮细胞以及新生血管平滑肌细胞均能产生BDNF,而且BDNF对血管内皮细胞的生长发育起着重要的支持作用[2,3].因此我们推测BDNF可能在一定程度上参与了机体新生血管的形成.为此,我们对BDNF的体内体外促血管新生作用进行了研究.
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先天性巨结肠神经胶质衍化亲神经营养因子的免疫组织化学观察
先天性巨结肠是儿科较常见的疾病,新生儿发病率为1/20 000~1/30 000.其病理表现主要为结肠远端神经节细胞的完全缺乏.现已证实,原癌基因RET是引起先天性巨结肠的主要基因,神经胶质细胞衍化亲神经营养因子(glial cell line derived neurotrophic factor,GDNF)是RET基因的配基之一[1].研究结果表明GDNF是有力的神经元的营养因子,可能与神经节细胞移行、分化过程有关.我们采用免疫组织化学方法,观察GDNF在先天性巨结肠各肠段的表达情况,探讨GDNF与先天性巨结肠发生的关系.
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血液中脑源性神经生长因子与疾病和运动的关系
脑源性神经生长因子(brain derived neurotrophic factor,BDNF)是体内含量高的生长因子之一,在人体中枢神经系统和血液中都有一定表达.人体神经系统和血液BDNF水平与许多神经系统疾病包括抑郁、阿尔茨海默病、精神分裂症及脑损伤和脊髓损伤功能恢复有关[1],BDNF还可以影响物质代谢和能量消耗,与糖尿病发生发展相关.运动可以影响神经系统和血液中BDNF的含量,从而在上述疾病的康复治疗中产生作用.BDNF联系了运动、神经功能和能量物质代谢,因此具有重要意义.本文主要总结血液中BDNF水平与运动和疾病的关系,以便更深入的探讨运动在这些疾病康复中的分子机制.
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神经生长因子的生物学效应及其在脑损伤康复中的研究进展
1神经生长因子的种类和生物学效应神经生长因子(nerve growth factor,NGF)是生长因子家族早发现的成员之一,由Rita Levi-Montgalcini在1953年首先发现.1986年Rita Levi-Montgalcini和Stanley Cohen因发现NGF和EGF(epidermal growth factor,EGF)被授予诺贝尔生物医学奖.NGF基因家族还包括BDGF(brain-derived neurotrophic factor)、neurotrophins-3和-4/5(NT-3,NT-4/5)和新近从鱼类中克隆得到的NT-6、NT-7[1].
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脑源性神经营养因子与缺血性脑卒中康复
缺血性脑卒中是在全球成人中患病率、死亡率、致残率都很高的疾病,因而其康复治疗十分重要,中国传统医学与现代康复治疗手段的结合已成为缺血性脑卒中康复治疗的重要发展方向[1].脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)是继神经生长因子(nerve growth factor,NGF)后第二个被发现的神经营养因子(neurotrophic factors,NTFs)家族成员,能支持多种神经元生存、发育、分化及修复.研究表明,BDNF在体内能营养某些对NGF无反应的感觉神经元,对胆碱能神经元、多巴胺能神经元、运动神经元等多种神经亚群具有重要的生物学功能,对脑卒中、脊髓损伤、神经系统退行性疾病及其他神经系统疾患所致的神经损伤具有潜在治疗作用[2].
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酪氨酸激酶受体和神经细胞黏附分子对老年大鼠黑质致密部多巴胺能神经细胞的影响
胶质细胞系源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)能有效地保护中脑黑质多巴胺能神经细胞[1],是迄今所发现的对多巴胺能神经细胞作用强的神经营养因子.
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丁苯酞对局灶性缺血预处理诱导脑缺血耐受影响的实验研究
丁苯酞是一种新型抗脑缺血药物,前期的研究已证实丁苯酞能够增强大鼠缺血预处理(ischemicpreconditioning,IP)后神经营养因子家族中的碱性成纤维细胞因子(bFGF)的表达[1].在此基础上,我们于2011年2月采用免疫组织化学方法检测神经营养因子家族中的另一成员——脑源性神经生长因子(brain-derived neurotrophic factor,BDNF)及其上游的转录调控因子磷酸化的环磷酸腺苷反应元件结合蛋白(phosphorylated cyclic AMP responsive element binding protein,p-CREB)在局灶性脑缺血耐受动物模型的脑梗死灶周围的表达,并采用蛋白质印迹(Western blotting)方法检测p-CREB/总cAMP反应元件结合蛋白(cAMP response element binding protein,CREB)表达,探讨丁苯酞局灶性缺血预处理诱导脑缺血耐受中可能的保护机制.
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胶质细胞源性神经营养因子及其受体过表达与胰腺癌生物学行为的关系
神经浸润是胰腺癌特征性浸润和转移方式,其转移率高达53%~100%,是影响胰腺癌患者预后的主要因素之一[1].但胰腺癌这种高度神经浸润特性的机制尚未完全清楚.近年研究表明胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)是TGF-β超家族的成员,而其受体RET(属于酪氨酸激酶)为RET原癌基因的产物,两者过表达与胰腺癌[2-3]及甲状腺癌[4-5]等肿瘤细胞增殖密切相关,但其过表达与胰腺癌的临床病理生物学行为的关系尚不清楚.本文通过检测胰腺癌组织GDNF及RET的蛋白表达情况,探讨GDNF及RET基因在胰腺癌发生发展过程中的作用及其对预后的影响.
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脑源性神经营养因子的临床应用前景
脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)是哺乳类动物脑内分布广、含量高的神经营养因子,人BDNF基因位于11q13.BDNF又是一种碱性蛋白质,由119个氨基酸残基组成.在不同物种间其氨基酸序列具有高度保守性,与神经营养因子(neurotrophic factor,NTF)家族其它成员序列同源性达50%~60%[1].BDNF分布主要集中在中枢神经系统,尤以大脑皮质及海马含量高,在周围系统,如心、肺、骨骼肌也有低水平表达.
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硫酸镁对新生鼠缺氧缺血性脑损伤保护作用的实验研究
缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)是严重威胁新生儿健康甚至致残的常见原因.为探讨HIBD有效的治疗手段,本实验利用新生大鼠HIBD模型,观察硫酸镁对脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)表达的影响和对受损神经元的保护作用.
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To evaluate the effects of glial cell line-derived neurotrophic factor transplantation combined with adipose-derived stem cells-transdifferentiated motoneuron delivery on spinal cord con-tusion injury, we developed rat models of spinal cord contusion injury, 7 days later, injected adipose-derived stem cells-transdifferentiated motoneurons into the epicenter, rostral and caudal regions of the impact site and simultaneously transplanted glial cell line-derived neuro-trophic factor-gelfoam complex into the myelin sheath. Motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery reduced cavity formations and increased cell density in the transplantation site. The combined therapy exhibited superior promoting effects on recovery of motor function to transplantation of glial cell line-derived neurotrophic factor, adipose-derived stem cells or motoneurons alone. These ifndings suggest that motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery holds a great promise for repair of spinal cord injury.
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Mecobalamin, a form of vitamin B12 containing a central metal element (cobalt), is one of the most important mediators of nervous system function. In the clinic, it is often used to accelerate recovery of peripheral nerves, but its molecular mechanism remains unclear. In the present study, we performed sciatic nerve crush injury in mice, followed by daily intraperitoneal administra-tion of mecobalamin (65 μg/kg or 130 μg/kg) or saline (negative control). Walking track analysis, histomorphological examination, and quantitative real-time PCR showed that mecobalamin signiifcantly improved functional recovery of the sciatic nerve, thickened the myelin sheath in myelinated nerve ifbers, and increased the cross-sectional area of target muscle cells. Further-more, mecobalamin upregulated mRNA expression of growth associated protein 43 in nerve tissue ipsilateral to the injury, and of neurotrophic factors (nerve growth factor, brain-derived nerve growth factor and ciliary neurotrophic factor) in the L4–6 dorsal root ganglia. Our ifndings indicate that the molecular mechanism underlying the therapeutic effect of mecobalamin after sciatic nerve injury involves the upregulation of multiple neurotrophic factor genes.
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Glial cell line-derived neurotrophic factor recombinant adenovirus vector-transfected bone marrow mesenchymal stem cells were induced to differentiate into neuron-like cells using inductive medium containing retinoic acid and epidermal growth factor. Cell viability, micro-tubule-associated protein 2-positive cell ratio, and the expression levels of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43 protein in the su-pernatant were signiifcantly higher in glial cell line-derived neurotrophic factor/bone marrow mesenchymal stem cells compared with empty virus plasmid-transfected bone marrow mes-enchymal stem cells. Furthermore, microtubule-associated protein 2, glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43 mRNA levels in cell pellets were statistically higher in glial cell line-derived neurotrophic factor/bone marrow mesen-chymal stem cells compared with empty virus plasmid-transfected bone marrow mesenchymal stem cells. These results suggest that glial cell line-derived neurotrophic factor/bone marrow mesenchymal stem cells have a higher rate of induction into neuron-like cells, and this enhanced differentiation into neuron-like cells may be associated with up-regulated expression of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43.
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Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Ad-ministration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In the rat model of depression established in this study, Shuganjieyu capsule was administered intragastrically daily before stress. Behavioral results conifrmed that depressive symptoms lessened after treatment with high-dose (150 mg/kg) Shuganjieyu capsule. Immunohistochemistry results showed that high-dose Shuganjieyu capsule signiifcantly increased phosphorylation levels of phosphorylation cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor expression in the medial prefrontal cortex and hippocampal CA3 area. Overall, our results suggest that in rats, Shuganjieyu capsule effec-tively reverses depressive-like behaviors by increasing expression levels of neurotrophic factors in the brain.
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Brachial plexus injury is frequently induced by injuries, accidents or birth trauma. Upper limb function may be partially or totally lost after injury, or left permanently disabled. With the de-velopment of various medical technologies, different types of interventions are used, but their effectiveness is wide ranging. Many repair methods have phasic characteristics, i.e., repairs are done in different phases. This study explored research progress and hot topic methods for pro-tection after brachial plexus injury, by analyzing 1,797 articles concerning the repair of brachial plexus injuries, published between 2004 and 2013 and indexed by the Science Citation Index database. Results revealed that there are many methods used to repair brachial plexus injury, and their effects are varied. Intervention methods include nerve transfer surgery, electrical stimula-tion, cell transplantation, neurotrophic factor therapy and drug treatment. Therapeutic methods in this ifeld change according to the hot topic of research.
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Human periodontal ligament stem cells are easily accessible and can differentiate into Schwann cells. We hypothesized that human periodontal ligament stem cells can be used as an alternative source for the autologous Schwann cells in promoting the regeneration of injured peripheral nerve. To validate this hypothesis, human periodontal ligament stem cells (1 × 106) were injected into the crush-injured left mental nerve in rats. Simultaneously, autologous Schwann cells (1 × 106) and PBS were also injected as controls. Real-time reverse transcriptase polymerase chain reaction showed that at 5 days after injection, mRNA expression of low affinity nerve growth factor receptor was sig-nificantaly increased in the left trigeminal ganglion of rats with mental nerve injury. Sensory tests, histomorphometric evaluation and retrograde labeling demonstrated that at 2 and 4 weeks after in-jection, sensory function was significantly improved, the numbers of retrograde labeled sensory neurons and myelinated axons were significantly increased, and human periodontal ligament stem cells and autologous Schwann cells exhibited similar therapeutic effects. These findings suggest that transplantation of human periodontal ligament stem cells show a potential value in repair of mental nerve injury.
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抑郁症与组织型纤溶酶原激活物及纤溶酶原系统功能紊乱
抑郁症是常见的精神疾病之一,普通人群的终身患病率一般在15%左右,女性高达25%.半个世纪以来,抑郁症生物学基础的主要解释是单胺递质异常假说,主要涉及去甲肾上腺素及5-羟色胺.近年来,多层面的研究显示,神经营养因子家族中的脑源性神经营养因子( brain derived neurotrophic factor,BDNF)在抑郁症发病以及抗抑郁药治疗机制中均起着重要作用[1].动物研究显示,环境应激可降低海马区BDNF的表达,而这一现象可被抗抑郁药逆转[2 ],并增加神经再生能力[3];给予应激抑郁模型动物外源性BDNF,也能产生抗抑郁作用.尸检研究显示,与生前未经抗抑郁药治疗的抑郁症患者相比,经药物治疗的患者海马区BDNF的免疫活性增加[4].临床研究显示,未接受抗抑郁药治疗的患者血清BDNF水平低于正常人,而抗抑郁药或电抽搐治疗后可恢复到正常范围[5-6].上述研究均提示,BDNF功能受损可能存在于抑郁症和应激相关的情感障碍,而上调BDNF可能是抗抑郁药发挥治疗作用的一个重要因素[7].因此,近年来围绕着抑郁症神经再生障碍假说和神经营养因子假说展开了大量的研究,其中抑郁症的组织型纤溶酶原激活物( tissue-type plasminogen activator,tPA)及纤溶酶原系统功能紊乱假说刚刚引起重视.本文就这一问题进行综述.
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精神分裂症和双相障碍患者认知功能障碍的遗传学研究进展
认知功能是大脑对信息加工处理的能力,即中枢神经系统分辨、整合信息并解决问题和完成任务的综合能力,涉及注意、词语与视觉记忆、视觉运动、语言、抽象思维、信息整合和运动及执行功能等多项内容.认知功能评估常采用神经心理测验,其中的方法很多,包括韦氏智力记忆量表中的各分测验、威斯康星卡片分类测验(Wisconsin Card SortingTest,WCST)、持续注意测验(Continuous Performance Test,CPT)、连线测验等.认知功能障碍常见于精神分裂症和双相障碍患者,遗传因素在认知功能的发生过程中起着重要的作用.近年来发现与精神分裂症和双相障碍认知功能相关的候选基因有很多,包括多巴胺系统基因、5-羟色胺(5-HT)系统基因、载脂蛋白E( apolipoprotein E,ApoE)、脑源性神经营养因子(brain derived neurotrophic factor,BDNF)基因等,现将这些基因进行分述.
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文拉法辛和帕罗西汀治疗中重度抑郁症的疗效与血浆脑源性神经营养因子水平变化的关系
近年来,脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)在抑郁症的发生和抗抑郁治疗中的作用越来越受到重视.我们就文拉法辛和帕罗西汀对中重度抑郁症疗效、对血浆BDNF水平的影响及二者的关系作了初步探索.对象抑郁症患者均来自湖州市第三人民医院神经症与心身疾病科、精神科病区,于2007年4月至2009年10月入组.入组标准:(1)符合中国精神障碍分类与诊断标准(第3版)抑郁发作的诊断标准;(2)基线17项汉密尔顿抑郁量表(HAMD17)评分≥25分;(3)年龄18~75岁,性别不限;(4)获得湖州市第三人民医院伦理委员会审核批准,所有患者签署书面知情同意书.排除标准:(1)入组前2个月服用其他影响精神活动的药物或任何抗抑郁药,或接受过电休克治疗,或正在接受系统的心理治疗;(2)妊娠或哺乳期妇女;(3)对药物过敏者;(4)有严重自杀倾向;(5)实验室及辅助检查有明显异常者.