脑红蛋白（NGB）神经保护机理与表达调控及其应用的初步研究
发布时间：2018-11-27 13:35
【摘要】：氧是生命活动的基本物质之一。神经系统的氧利用问题更是关乎机体健康与否的重要科学命题。2000年Burmester等首次报道,脑内存在第三种携氧珠蛋白——脑红蛋白(NGB),为神经系统氧利用的研究带来新的曙光。为了深入研究NGB与神经系统氧利用的关系,本课题进行三方面研究: 首先,采用一系列生物化学技术证明了脑红蛋白与Na~+,K~+-ATPase 1 β2亚基(NKA1b2)之间存在相互作用,在此基础上提出了全新假说“能量保全可能是神经保护的一个重要策略”,为神经保护研究领域提供了新观点,并为研发全新的神经保护药物用于脑卒中等疾病的治疗提供了新的方向。进一步,由于目前认为脑红蛋白可能是参与神经保护的一个重要分子,本文又初步研究了其上游表达调控信号。结合生物信息学研究,通过实验初步显示P53可能是调节脑红蛋白表达水平的一个重要因子。这一研究为剖析以脑红蛋白为中心的神经保护分子调控网络提供了重要证据。在对脑红蛋白神经保护功能研究的基础上,为了尽快实现基础研究与临床应用之间的对接,在成功制备抗脑红蛋白多克隆抗体和单克隆抗体的基础上,进一步研制了具有较高灵敏度的双抗夹心ELISA检测试剂盒并已申报国家发明专利,目前已经用于脑缺血损伤与保护动物模型以及临床上血清标本中脑红蛋白含量的检测工作。 综上所述,本研究揭示了脑红蛋白神经保护功能的可能机制,为基于此保护机制研发新的神经保护药物用于脑卒中的治疗奠定了基础,并初步实现了从基础研究向临床应用的过渡。在此基础上,预期将有可能建立以脑红蛋白为核心的神经损伤与神经保护的理论体系,并将为临床实践中提供全新的神经保护策略提供重要参考价值。
[Abstract]:Oxygen is one of the basic substances of life. The problem of oxygen utilization in the nervous system is an important scientific proposition related to the health or not of the body. In 2000, Burmester et al first reported that the existence of a third oxygen-carrying globin (NGB), in the brain brings a new dawn to the study of oxygen utilization in the nervous system. In order to study the relationship between NGB and oxygen utilization in the nervous system, three aspects were studied. Firstly, a series of biochemical techniques were used to prove the relationship between brain erythroprotein and Na~. Based on the interaction between K- ATPase 1 尾 2 subunit (NKA1b2), a new hypothesis that energy preservation may be an important strategy of nerve protection is proposed, which provides a new viewpoint for the field of neuroprotection. It provides a new direction for the development of new neuroprotective drugs for the treatment of stroke and other diseases. Furthermore, as it is believed that the brain protein may be an important molecule involved in neuroprotection, the upstream expression and regulatory signals are studied preliminarily in this paper. In combination with bioinformatics studies, we preliminarily indicated that p53 may be an important factor in regulating the expression of brain erythroprotein. This study provides important evidence for the analysis of neuroprotective molecular regulatory networks centered on neuroglobin. In order to realize the docking between basic research and clinical application as soon as possible, on the basis of the study of neuroprotective function of brain hemoglobin, the polyclonal antibody and monoclonal antibody against brain hemoglobin were successfully prepared. Furthermore, a high sensitivity double antibody sandwich ELISA detection kit has been developed and applied for the detection of brain erythroprotein in cerebral ischemia injury and protection animal models and clinical serum samples. To sum up, this study revealed the possible mechanism of neuroprotective function of brain erythrin, which laid a foundation for the development of new neuroprotective drugs for stroke treatment. The transition from basic research to clinical application has been preliminarily realized. On this basis, it is expected that it will be possible to establish a theoretical system of nerve injury and nerve protection with the brain protein as the core, and to provide an important reference value for the clinical practice of a new neuroprotective strategy.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：Q593.2
[Abstract]:Oxygen is one of the basic substances of life. The problem of oxygen utilization in the nervous system is an important scientific proposition related to the health or not of the body. In 2000, Burmester et al first reported that the existence of a third oxygen-carrying globin (NGB), in the brain brings a new dawn to the study of oxygen utilization in the nervous system. In order to study the relationship between NGB and oxygen utilization in the nervous system, three aspects were studied. Firstly, a series of biochemical techniques were used to prove the relationship between brain erythroprotein and Na~. Based on the interaction between K- ATPase 1 尾 2 subunit (NKA1b2), a new hypothesis that energy preservation may be an important strategy of nerve protection is proposed, which provides a new viewpoint for the field of neuroprotection. It provides a new direction for the development of new neuroprotective drugs for the treatment of stroke and other diseases. Furthermore, as it is believed that the brain protein may be an important molecule involved in neuroprotection, the upstream expression and regulatory signals are studied preliminarily in this paper. In combination with bioinformatics studies, we preliminarily indicated that p53 may be an important factor in regulating the expression of brain erythroprotein. This study provides important evidence for the analysis of neuroprotective molecular regulatory networks centered on neuroglobin. In order to realize the docking between basic research and clinical application as soon as possible, on the basis of the study of neuroprotective function of brain hemoglobin, the polyclonal antibody and monoclonal antibody against brain hemoglobin were successfully prepared. Furthermore, a high sensitivity double antibody sandwich ELISA detection kit has been developed and applied for the detection of brain erythroprotein in cerebral ischemia injury and protection animal models and clinical serum samples. To sum up, this study revealed the possible mechanism of neuroprotective function of brain erythrin, which laid a foundation for the development of new neuroprotective drugs for stroke treatment. The transition from basic research to clinical application has been preliminarily realized. On this basis, it is expected that it will be possible to establish a theoretical system of nerve injury and nerve protection with the brain protein as the core, and to provide an important reference value for the clinical practice of a new neuroprotective strategy.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：Q593.2
【引证文献】
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1 尹静;张祥建;李俐涛;杨q，
本文编号：2360967
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