重组人干扰素α-2b联合盐酸伐昔洛韦片治疗老年人带状疱疹临床疗效观察

目的观察比较重组人干扰素α-2b联合盐酸伐昔洛韦片与单用盐酸伐昔洛韦片治疗老年带状疱疹患者效果。方法将2010-2014年收治的66例带状疱疹患者随机分为观察组和对照组;观察组32例,对照组34例。观察比较两组患者接受治疗前后临床指标、治疗过程中副反应、临床疗效及带状疱疹后遗神经痛发生率等情况。结果 1观察组疗效明显优于对照组(P<0.05)。2治疗后,观察组疼痛评分低于对照组(P<0.05)。3治疗后,两组患者的后遗神经痛发生率比较差异无统计学意义(P>0.05)。结论重组人干扰素α-2b联合盐酸伐昔洛韦片治疗老年带状疱疹疗效优于单用盐酸伐昔洛韦片,且未增多药物副反应。但对减少带状疱疹后遗神经痛方面未发现明显效果。     

阿尔兹海默症动物模型的研究进展

摘要: 阿尔兹海默病( Alzheimer’s disease ,AD) ,是一种中枢神经系统进行性退行性疾病。由于发病机制复杂,发病原因多样,制约了其动物模型研究的发展,本文将阿尔兹海默症动物模型分为转基因动物模型与非转基因动物模型,并具体介绍了APP 转基因小鼠模型、APP/PSI 双转基因小鼠模型、Tau /APP/PSI 三转基因小鼠模型三种转基因动物模型,以及Aβ 诱导的AD 动物模型等六种非转基因动物模型。与此同时就其动物模型的优缺点进行了总结,并对未来发展趋势做出展望。     

脑组织特异性表达胰岛素样生长因子-1转基因小鼠制备

目的制备脑组织特异性表达胰岛素样生长因子-1(Insulin-Like Growth Factors 1,IGF-1)转基因小鼠。方法采用精子为载体法进行基因转导,出生后小鼠PCR检测,建立转基因小鼠系,用Western blot和免疫荧光法分别检测转基因小鼠海马齿状回亚粒状区(subgranular zone,SGZ)IGF-1表达量和报告基因EGFP阳性细胞数。结果获得3只阳性小鼠,2只外源基因能稳定遗传,并建立了转基因小鼠系,转基因鼠SGZ区域IGF-1表达量显著高于正常鼠,EGFP也在此区域表达。结论成功制备IGF-1转基因小鼠。     

盐酸伐昔洛韦片联合匹多莫德片治疗复发性生殖器疱疹的观察

目的:评价口服盐酸伐昔洛韦片联合口服匹多莫德片治疗复发性生殖器疱疹的临床疗效。方法:选择复发性生殖器疱疹患者88例,随机分为两组,治疗组45例,对照组43例。治疗组采用口服盐酸伐昔洛韦片联合口服匹多莫德片联合治疗,对照组单纯口服盐酸伐昔洛韦片治疗,疗程均2个月,随访6个月。结果:总体效果评价中,治疗组和对照组总有效率分别为97.8%、95.4%,两组疗效差异无显著性(P>0.05),治疗组和对照组复发率分别为53.3%、90.7%,治疗组复发率明显低于对照组,差异有显著性(P<0.01)。患者均未见明显不良反应。结论:口服盐酸伐昔洛韦片与口服匹多莫德片联合治疗复发性生殖器疱疹疗效好,且复发率明显低于单纯口服盐酸伐昔洛韦片,是治疗复发性生殖器疱疹较好的方法之一。     

青光眼动物模型研究进展

青光眼是一种不可逆性视神经退行性病变,为全球第二位致盲眼病。在青光眼研究领域,动物模型已成为重要的研究工具。青光眼动物模型对于更好的理解青光眼性视神经病变的损伤机制及治疗措施有着重要的作用。目前研究中使用最多的动物主要有鼠、兔、猴。本综述较全面系统地概述了各种青光眼动物模型的研究进展,包括近年来发展的转基因鼠青光眼模型,如急性高眼压转基因小鼠CLR(calcitonin receptor-like receptor)、利用基因打靶技术构建的自然青光眼模型等,并分别对各种模型在视网膜神经节细胞(RGCs)、视神经、视网膜功能方面的研究做了介绍,分析各种模型的利与弊,为在青光眼研究中更好地选择合适的模型提供依据。     

伐昔洛韦联合氦氖激光治疗带状疱疹临床观察疗效

目的:探讨伐昔洛韦联合氦氖激光治疗带状疱疹的临床疗效.方法:选择门诊及住院带状疱疹患者60例,随机分成观察组和对照组,每组30例.对照组给予口服伐昔洛韦500 mg/次,3次/d,口服布洛芬缓释胶囊每次1粒,每日1次/d;辅以营养神经药物.观察组在对照组治疗基础上局部采用氦氖激光治疗仪治疗,波长632.8 nm.根据皮损面积分片照射,每处每次照射10～15 min,1次/d,10次为1疗程.两组均以10d为1疗程.观察患者治疗前和治疗开始时患者疼痛程度、疼痛缓解时间、止庖时间、50％皮疹结痂时间、皮损消退时间、总有效率及不良反应.结果:治疗后在疼痛程度、疼痛缓解时间,观察组与对照组比较差异有统计学意义(p＜0.05);治疗开始后患者在止庖时间、50％皮疹结痂时间、皮损消退时间观察组优于对照组,两组比较差异有统计学意义(p＜0.05);临床疗效,观察组总有效率为86.7％,对照组总有效率为70％,两组比较差异有统计学意义(p＜0.05).结论:伐昔洛韦联合氦氖激光治疗治疗带状疱疹安全、疗效确切,起效快.     

伐昔洛韦联合微米光治疗28例带状疱疹的临床观察

目的:观察伐昔洛韦(valacyclovir)联合微米光治疗28例带状疱疹的临床疗效.方法:将54例带状疱疹患者随机分为两组,试验组28例口服伐昔洛韦(商品名:维德思)1 000 mg,每日3次,共服7d后改为每次500 mg,每日3次,继续服用7d.同时皮肤照射微米光每日一次,共照射14 d.对照组26例口服阿昔洛韦,200 mg,每日5次,同样每日照射微米光,与试验组一致,共14 d.观察记录第1、3、5、7、10、14天时止疱、结痂、疼痛及不良反应,第14天根据评分表评定总疗效.结果:试验组痊愈率为82.1％,对照组为46.2％,差异有统计学意义(P＜0.01),试验组有效率为96.4％,对照组为73.1％ (P ＜0.05).全部患者无严重不良反应发生,疗程结束后查肝肾功能无明显改变.结论:伐昔洛韦(维德思)联合微米光能明显缩短带状疱疹病程、加快水疱干枯结痂、促进皮损愈合、减少神经痛的程度及持续时间,降低后遗神经痛的发生率.     

APP/PS1双转基因小鼠鉴定及生物学功能研究

通过对APP/PS1双转基因小鼠尾部组织进行DNA提取,后续采用PCR扩增、琼脂凝胶电泳实验方法进行条带分析鉴定,比较蛋白酶K法和碱裂法对DNA提取差异,通过行为学实验、免疫荧光实验和Western blot检测小鼠病理产物的表达以验证APP/PS1双转基因小鼠生物学功能改变.结果显示,与蛋白酶K法相比,碱裂法提取的DNA浓度明显较高(P<0.001),纯度无显著性差异(P>0.05).水迷宫行为检测结果显示,定位航行实验中,与野生型比较,两组APP/PS1小鼠平均逃避潜伏期明显延长(P<0.05,P<0.01,P<0.001),空间探索实验中,与野生型比较,两组APP/PS1小鼠穿越平台次数明显减少(P<0.05,P<0.01),目标象限停留时间明显缩短(P<0.01).Y迷宫实验结果显示,与野生型比较,两组APP/PS1转基因小鼠自发交替准确率明显降低(P<0.01).免疫荧光实验结果显示,与野生型小鼠比较,两组APP/PS1转基因小鼠脑部明显产生Aβ沉积(P<0.01,P<0.001).Western blot结果显示,与野生型比较,两组APP/PS1转基因小鼠海马组织Aβ表达量明显增多(P<0.05).以上结果表明,APP/PS1双转基因小鼠在8月龄出现明显Aβ沉积及行为学改变,在DNA提取方面,蛋白酶K法和碱裂法对APP/PS1双转基因小鼠的DNA提取均准确无差异,碱裂法具有简单高效的优点,在常用的定性鉴定方面具有优势.     

Foxo1突变体转基因,ob/ob小鼠建立与表型分析

Foxo1是瘦素作用的负调控因子,实验室前期工作发现,其突变体Foxo1ΔDBD可导致转基因小鼠体重降低等表现型,本实验旨在研究转基因小鼠此表型与瘦素作用的关系.首先采用ALZET?渗透泵的方法对成年雄性的具有瘦素基因缺陷(ob/ob)小鼠进行10 d的瘦素处理,使其获得生育能力,然后采用动物杂交的方法制备双基因改造鼠,即ob/ob基因遗传背景的Foxo1ΔDBD转基因小鼠(Foxo1ΔDBD/+,ob/ob).经PCR扩增的方法进行基因型鉴定后,对双基因改造鼠的体重、体温等表型进行分析.结果显示:①植入含瘦素溶液的ALZET?渗透泵10 d后的4只雄性ob/ob小鼠全部获得了生育能力.②成功制备了46只双基因改造鼠,39只ob/ob小鼠等.③表型分析结果显示,无ob/ob遗传背景的转基因Foxo1ΔDBD小鼠(Foxo1ΔDBD/+)与野生型小鼠相比,体重显著性降低(P0.05),棕色脂肪内的UCP1转录水平显著升高(P0.05);而双基因改造鼠和ob/ob小鼠相比,体重、体温、空腹血糖和采食量均无显著性差异(P0.05),且UCP1转录水平上的表达也无显著性差异(P0.05).本实验成功制备了双基因改造鼠,并进行了表型分析,结果表明Foxo1ΔDBD转基因小鼠的体重降低和棕色脂肪UCP1转录升高等表现依赖瘦素的作用.     

淫羊藿黄酮对APP转基因小鼠学习记忆及β-amyloid生成的影响

观察不同月龄APP(amyloid precursor protein)转基因模型小鼠学习记忆功能的改变,以及中药有效部位淫羊藿黄酮对10月龄转基因小鼠学习记忆功能和脑内APP、BACE的表达及β-淀粉样肽(β-amyloid,Aβ)生成及含量的影响.用药组小鼠自4月龄开始灌胃给予淫羊藿黄酮小(0.03 g·kg-1/d)、大剂量(0.1 g·kg-1/d)6个月至10月龄,正常对照组、转基因阴性对照组及模型组以同样方式灌胃给予蒸馏水.应用Morris水迷宫和物体识别方法测试小鼠学习记忆能力,应用免疫组化学及Western Blot方法分别检测海马CA1区及皮层中APP、BACE的表达,采用双抗体夹心ELISA试剂盒测定海马中不溶性Aβ1-42含量.研究结果表明,APP转基因小鼠在4月龄即出现学习记忆能力障碍,在水迷宫实验中,比转基因阴性对照组小鼠潜伏期延长28%(p<0.05).增龄至10月龄,APP转基因小鼠学习记忆能力明显下降,水迷宫潜伏期及游泳距离与转基因阴性对照组的差异分别加大为40%(p<0.01)和35%(p<0.05),物体识别实验中分辨指数的差异为61%(p<0.05).与正常对照组及转基因阴性对照组相比,10月龄转基因模型小鼠海马CA1区及皮层中APP和BACE的表达明显增加,海马中Aβ1-42的含量明显升高.淫羊藿黄酮大剂量可明显改善10月龄APP转基因小鼠Morris水迷宫作业成绩,提高模型鼠物体识别能力,明显减少APP转基因模型小鼠海马和皮层APP及BACE的表达,降低海马Aβ1-42的含量.提示淫羊藿黄酮能改善APP转基因模型小鼠学习记忆能力和减少Aβ经由淀粉源途径生成及含量,对防治AD等神经退行性疾病具有良好的应用前景.     

Long-term regenerated nerve fibres retain sensitivity to potassium channel blocking agents

Mammalian myelinated peripheral nerve fibres display a remarkable degree of regeneration following a discrete nerve crush. Nerve crush disrupts the axon cylinder, but leaves the basement membrane of the Schwann cell intact. These intact endoneurial tubes provide pathways to guide the regenerating axon sprouts. After contact with the periphery is established, the regenerating fibres enlarge and myelinate. Conduction velocity recovers to nearly normal and functional recovery is, in many cases, nearly complete. A distinct feature of normal mature myelinated axons is the insensitivity of these fibres to potassium channel blocking agents. In contrast, immature myelinated axons are exquisitely sensitive to the K channel blocking agent 4-aminopyridine (4-AP). Application of 4-AP to immature myelinated fibres leads to a delayed membrane depolarization with action potential burst activity in response to a single stimulus. This sensitivity to 4-AP is attenuated as the fibres mature. Previous studies have demonstrated a sensitivity to 4-AP in regenerating nerve fibres; this sensitivity differentiates the regenerating axon segments from their normal parent axon segments. Such studies have not, however, examined the question of whether regenerated fibres, which have re-established peripheral connections and are functionally active, fully recapitulate the functional organization of normal mature myelinated fibres. We demonstrate here that while sensitivity to the potassium channel blocking agents 4-AP and 3, 4-diaminopyridine (3, 4-DAP) is lost in the normal course of myelinated axon maturation, this property is present in long-term regenerated axons. This suggests that long-term regenerated mammalian axons are characterized by a functional organization that bears a closer resemblance to that of immature myelinated fibres than to that of adult myelinated fibres.     

鱼类视神经损伤和再生的研究

综述了鱼类视网膜－顶盖系统的研究概况，包括视网膜、视神经和顶盖的组织结构特点；同时介绍了损伤视神经引起的视网膜神经节细胞的变化及其跨神经元的影响；最后综述了视神经再生与神经传入活性、相邻神经纤维间的相互作用及靶区选择的关系等方面的研究进展     

Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein

Adult mammalian axon regeneration is generally successful in the peripheral nervous system (PNS) but is dismally poor in the central nervous system (CNS). However, many classes of CNS axons can extend for long distances in peripheral nerve grafts. A comparison of myelin from the CNS and the PNS has revealed that CNS white matter is selectively inhibitory for axonal outgrowth. Several components of CNS white matter, NI35, NI250(Nogo) and MAG, that have inhibitory activity for axon extension have been described. The IN-1 antibody, which recognizes NI35 and NI250(Nogo), allows moderate degrees of axonal regeneration and functional recovery after spinal cord injury. Here we identify Nogo as a member of the Reticulon family, Reticulon 4-A. Nogo is expressed by oligodendrocytes but not by Schwann cells, and associates primarily with the endoplasmic reticulum. A 66-residue lumenal/extracellular domain inhibits axonal extension and collapses dorsal root ganglion growth cones. In contrast to Nogo, Reticulon 1 and 3 are not expressed by oligodendrocytes, and the 66-residue lumenal/extracellular domains from Reticulon 1, 2 and 3 do not inhibit axonal regeneration. These data provide a molecular basis to assess the contribution of Nogo to the failure of axonal regeneration in the adult CNS.     

外周神经的溃变与再生

本文阐述了外周神经溃变的几种类型,诸如顺行性变性;逆行性变性;跨神经元变性及其它变性.其中包括外周神经系统的变性,也涉及到中枢神经系统.当轴突受到破坏后,几种变性都可能发生.轴突的再生过程非常重要,但它必须是在神经元胞体完好无损的情况下才能进行.此过程与几种因素相关.     

花背蟾蜍蝌蚪视神经再生与角膜诱导间关系的研究

以花背蟾蜍（Bufo raddei Srauch)后肢芽期蝌蚪为材料,切断其左眼视神经并进行角膜移植,在角膜诱导的不同时期取眼球固定,用环氧树脂Epon812包埋,制成兰薄切片,用次甲蓝、天青Ⅱ、硼砂染色后,在光学显微镜下观察切断视神经后视网膜的退化过程及在视神经再生的情况下视网膜诱导皮肤移植片转化为角膜的作用。结果表明,切断视神经,引起视网膜逐渐退化,移植的皮肤片与正常的皮肤其本相似;在分断的视神经发生再生并恢复其正常的生理功能的情况下,退化的视网膜逐渐恢复,同时被移植的皮肤片也出现表皮的去分化及表皮变薄等被诱导为角膜的过程,并对视神经的完整性与其诱导皮肤移植片转化为角膜之间的可能关系进行了讨论。     

Dog sciatic nerve gap repaired by artificial tissue nerve graft

The feasibility of repairing dog sciatic nerve damage by using a biodegradable artificial tissue nerve graft enriched with neuroregenerating factors is investigated. The artificial nerve graft was implanted to a 30 mm gap of the sciatic nerve damage in 7 dogs. The dogs with the same nerve damage that were repaired by interposition of the autologous nerve or were given no treatment served as control group 1 or 2, respectively. The observations include gross and morphological observations, immune reaction, electrophysiological examination, fluorescence tracing of the neuron formation and the number of the neurons at the experimental sites, etc. Results showed that 6 months after the implantation of the graft, the regenerated nerve repaired the damage of the sciatic nerve without occurrence of rejection and obvious inflammatory reaction in all 7 dogs, and the function of the sciatic nerve recovered with the nerve conduction velocity of (23.91±11.35)m/s. The regenerated neurons and the forming of axon could be observed under an electron microscope. This proves that artificial tissue nerve graft transplantation can bridge the damaged nerve ends and promote the nerve regeneration.     

Experimentally induced alteration in the polarity of developing neurons

Despite the great diversity of shapes exhibited by different classes of nerve cells, nearly all neurons share one feature in that they have a single axon and several dendrites. The two types of processes differ in their morphology, in their rate of growth, in the macromolecular composition of their cytoskeletons and surface membranes, and in their synaptic polarity. When hippocampal neurons are dissociated from the embryonic brain and cultured, they reproducibly establish this basic form with a single axon and several dendrites, despite the absence of any spatially organized environmental cues, and without the need for cell to cell contact. We have cut the axons of young hippocampal neurons within a day of their development: in some cases the initial axon regenerated, but more frequently one of the other processes, which if undisturbed would have become a dendrite, instead became the axon. Frequently the stump of the original axon persisted following the transection and subsequently became a dendrite. Evidently the neuronal processes that first develop in culture have the capacity to form either axons or dendrites. The acquisition of axonal characteristics by one neuronal process apparently inhibits the others from becoming axons, so they subsequently become dendrites.     

视神经损伤引起斑马鱼视网膜神经细胞凋亡的研究

用石蜡连续切片苏木精染色法,通过定量分析研究夹伤和切断视神经后,斑马鱼视网膜神经节细胞、视杆和视锥细胞密度的变化。结果发现,在损伤视神经7～21d后,上述3种细胞的细胞核密度均呈减少趋势,节细胞减少的比率大于感光细胞,而感光细胞中视锥细胞所受影响比视杆细胞更为明显;在夹伤和切断视神经两种情况中,后者引起视网膜神经节细胞核密度的减少更为显著。上述结果表明,损伤视神经不但影响与其相连的神经节细胞,而且可逆向跨神经元地影响感光细胞的变化。由上述结果推测,由于损伤视神经使视网膜神经节细胞失去靶组织而引起的各种神经细胞密度减少是视网膜中神经细胞凋亡的表现。     

降钙素基因相关肽在受损SD大鼠面神经运动神经元中的表达与定位

目的：研究降钙素基因相关肽（calcitonin gene—related peptide。CGRV）在面神经损伤后再生过程中面神经运动神经元中的表达变化．方法：健康SD大鼠分别行左侧面神经茎乳孔压榨术,术后饲养3、7、14、21、28、35d,取出脑干含面神经核团部分,用免疫组化及图像分析技术,观察面神经核中的CGRP在面神经再生中的变化．结果：CGRP分布于正常SD大鼠面神经各亚核。面神经损伤后3d。损伤侧的面神经核中CGRP比对照侧增强．图像分析CGRP灰度值与对照侧比较,差异显著（P〈0．05）;损伤后7d达最高峰（P〈0．05）,以后尽管显著表达但渐减．结论：损伤导致CGRP在面神经运动神经元中的表达增加,提示CGRP在面神经再生修复过程中发挥调理作用．