帕金森病治疗的新策略

以左旋多巴为主的替代疗法仍然在当今临床治疗帕金森病中扮演主要角色。近年来随着现代科技的发展和人们对帕金森病发病的病因和病理的再认识,以神经保护性治疗为主的一些新的治疗方案正日渐成熟并在逐步走向临床,而与此同时另一些新的治疗方案和药物正在不断被提出和研制。可以预期这些新疗法的实施将会为有效地缓解帕金森病病人的痛苦和延缓疾病的进展作为贡献。本文旨的对方面的研究作一介绍。     

神经退行性疾病病变机理及药物作用新靶点

神经退行性疾病是医学研究领域中的一大难题,近年来,该类疾病遗传因素及病变机理的研究取得了很大进展。研究表明这类疾病的发生与某些基因突变后产生的蛋白有关,这些蛋白可进而直接或间接地引起一系列反应,影响神经系统中某些特定的神经细胞,最终导致这些细胞死亡。     

感应电检测技术在面瘫治疗中的应用

作者在近五年针灸理疗工作中，曾先后接诊过６位面神经麻痹病人，经过用针、电等综合方法治疗，并运用ＤＬ—Ⅱ型直流感应电疗机，应用感应电技术，以客观指标来指导针炙合理选穴以进行治疗，效果满意。     

用于标定和优化的高压共轨柴油机建模

高压共轨柴油机可控燃油喷射参数的增加,在使对燃烧的控制更加灵活的同时也带来标定和优化工作量显著增加的问题.为适应高效率的需要,提出并研究了基于模型的标定优化,即采用神经网络在一些工况点上建立模型,再通过自适应神经模糊推理系统(ANFIS)进行插值,将模型由这些工况点扩展到所需工况空间.模型精度由对象、建模所用数据量及模型参数调整共同决定.试验在一台六缸高压共轨柴油机上进行.理论分析和试验结果表明 该方法可以在保证精度的同时有效减少标定优化的试验工作量.     

Regulation of BMP4 on the proliferation and differentiation in SVZa neural stem cells

The neural stem cells in the anterior subventricular zone (SVZa) mainly generate the progenitors that will differentiate into neurons, and along a highly circumscribed migratory access Rostral migratory stream (RMS), they migrate to the olfactory bulbs (OB). To understand the effects of BMPs on SVZa neural stem cells, in this study BMP4 at various concentrations was used to induce SVZa neural stem cells, and the living cell labeling using BMP4 promotor conjugated with red fluorescence protein showed the expression of BMP4 dynamically. The results demonstrated that low BMP4 doses (1-5 ng/mL) promoted while high doses (10-100 ng/mL) inhibited the proliferation of SVZa neural stem cells, and BMP4 promotedneuron differentiation in the early stage (1-3 d), howeverm, it inhibited the neuron commitment after 4 d. Noggin, the antagonist of BMP4, blocked the physiological effects of BMP4. In OB, BMP4 is mainly to accelerate the progenitors to withdraw from the cell cycle and trigger the differentiation, and in RMS, it promotes the proliferation of committed progenitors and not differentiation, further in SVZa, BMP4 enhances astrocyte commitment.     

GFP标记的GDNF重组腺病毒载体的构建和体内外表达

通过构建绿色荧光蛋白(GFP)和胶质细胞源性神经营养因子(GDNF)共表达的腺病毒载体,讨论其在治疗脊髓和脑有关神经系统疾病的潜在应用价值,了解腺病毒载体在大鼠体内的分布及在体外分泌外源基因产物能力,并对其生物安全性作了初步考察,为GDNF重组腺病毒载体在临床和基础研究中的应用作了一定准备．     

抗坏血酸定向诱导神经干细胞分化为多巴胺能神经细胞及其机理研究

神经干细胞(NSCs)是神经系统发生的始祖细胞,具有自我更新和多向分化潜能.NSCs的研究不仅对阐明神经系统发育有重要意义,对神经系统疾病的治疗也提出了新的思路.研究NSCs定向分化的诱导因素和机制对NSCs的应用具有重要意义.本实验在体外神经干细胞培养鉴定和扩增的基础上,观察了抗坏血酸(AA)对NSCs定向诱导分化作用,并探讨了分化过程中相关基因表达的变化和可能的信号传递途径.结果表明AA诱导能明显促进多巴胺能神经细胞特异性酪氨酸羟化酶(TH)、多巴胺转运子(DAT)mRNA和蛋白表达;NSCs表达Ptx3和较弱的Nurr1,不表达TH,DAT和Shh;诱导后Ptx3表达无变化,Nurr1,Shh,TH和DAT表达增强.Erk阻断剂PD98059能阻断AA对Nurr1,TH,DAT mRNA的作用.提示Nurr1参与AA定向诱导,AA可能通过Erk1/2信号转导途径起作用.研究为获得足够的治疗帕金森氏病的多巴胺能神经元提供了新的思路,并对AA定向诱导的机制进行了初步研究,对更好地发挥NSCs移植治疗帕金森氏病具有重要意义.     

Modulation of presynaptic nAChRs on postsynaptic GABA receptor in optic tectum of juvenile<Emphasis Type="Italic">Xenopus</Emphasis>

Using the blind patch-clamp technique with the whole-cell mode,we have studied the modulation presynaptic receptor on postsynaptic γ-raminobutyric acid (GABA) receptor measuring miniature inhibitory postsynaptic currents (mIPSCs)in optic tectum of Xenopus during critical peroid.It was demonstrated that compared with mature neurons,mIPSCs recorded from immature neurons had smaller amplitude and longer decay time.mIPSCs are mediated by GABAa receptor.The nicotinic acetylcholine receptor agonists(carbachol,cytisine,nicotine,DMPP and so on) could increase the frequency of mIPSCs.The enhancement of mIPSCs frequency induced by nAChR agonists was calcium-dependent.However,the choline,a product of hydrolyzed acetylcholine,could not increase the frequency of mIPSCs.DH-β-E,a competitive antagonist of nAChR,blocked the increase of mIPSCs frequency induced by carbachol.Mecamyllamine,an α3β4 subtype of nAChR antagonist,also blocked the carbachol-induced enhancement of mIPSCs.On the other hand,MLA,α7 subtype of nAChR antagonist,had no effect on it .Thus,it seems that nAChR could presynaptically modulate the mIPSCs and α3β4 subtype of nAChR might be involved.But α7 nAChR subtype of nAChR would not be involved.The modulation is calcium-dependent.Meanwhile,we found that Ca^2 -free solution could elicit giant PSCs.The frequency of mIPSCs also is related with the level of HP.