联合应用NGF和GM1对神经元损伤保护作用的实验研究

发布时间：2018-09-12 05:37

【摘要】：神经生长因子(nerve growth factor,NGF)不仅对正在发育的神经系统中神经元的存活、分化和成熟等方面产生重要影响，而且在动物的整个生命过程中起着广泛的作用。近年来，有许多研究证明，，NGF对受刺激或损伤的背根神经节(dorsal root ganglion，DRG)神经元、脊髓神经元结构及功能的可塑性具有影响，NGF能够介导DRG神经元和脊髓神经元的细胞内事件，如神经元突起内线粒体的运输或聚集以及细胞内钙离子浓度的变化等。神经系统受损伤以后NGF的表达增加，这对于神经系统正常结构和功能的维持是必须的。总之，NGF对受损伤的神经元具有保护作用。单涎性神经节苷脂(monosiaganglioside，GM1)在神经系统发育过程中，在含量上具有显著的变化。体内与体外实验皆表明，神经细胞分化过程中伴随着GM1生物合成的改变。神经细胞诱导分化过程中伴有核膜GM1含量的增高。GM1通过影响由多肽生长因子调控的细胞增殖和促成熟过程而调节细胞生长。在DRG神经元突起的发芽和生长过程中，NGF和GM1共同作用介导了这一过程。联合应用NGF和GM1对神经元的保护作用机制目前尚不清楚。因此，本研究将原代分散培养的胎鼠DRG神经元和脊髓神经元，用谷氨酸(2mmol／L)造成神经元损伤，观察联合应用NGF和GM1对体外培养神经元损伤的保护作用，并探讨其作用机制；将成年大鼠坐骨神经造成缺损，使其相应节段的DRG神经元和脊髓前角神经元产生损伤，探讨联合应用NGF和GM1对在体神经元损伤的保护作用。结果表明联合应用NGF和GM1对DRG神经元和脊髓神经元的保护作用效果明显优于单纯应用
[Abstract]:Nerve growth factor (nerve growth factor,NGF) not only plays an important role in the survival, differentiation and maturation of neurons in the developing nervous system, but also plays an important role in the whole life process of animals. In recent years, many studies have shown that NGF has an effect on the plasticity of the structure and function of the stimulated or injured dorsal root ganglion (dorsal root ganglion,DRG) neurons and spinal cord neurons. NGF can mediate intracellular events in DRG neurons and spinal cord neurons. Such as the transport or aggregation of mitochondria in neurite and the change of intracellular calcium concentration. The expression of NGF is increased after nervous system injury, which is necessary for the maintenance of normal structure and function of nervous system. NGF can protect injured neurons. Monolabar ganglioside (monosiaganglioside,GM1) has a significant change in the content of the nervous system during the development of the nervous system. In vivo and in vitro experiments showed that GM1 biosynthesis was associated with neuronal differentiation. During the induction of neuronal differentiation, the nuclear membrane GM1 content is increased. GM1 regulates cell growth by affecting the proliferation and maturation process regulated by polypeptide growth factor. This process is mediated by the interaction of DRG and GM1 during the germination and growth of neuronal processes. The protective mechanism of combined use of NGF and GM1 on neurons is unclear. Therefore, the primary cultured fetal DRG neurons and spinal cord neurons were treated with glutamic acid (2mmol/L) to induce neuronal injury. The protective effects of NGF and GM1 on cultured neurons were observed and its mechanism was discussed. The sciatic nerve in adult rats was damaged by DRG neurons and spinal cord anterior horn neurons. The protective effects of NGF and GM1 on in vivo neuronal injury were investigated. The results showed that the protective effect of combined application of NGF and GM1 on DRG neurons and spinal cord neurons was better than that of single application.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R363

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