【摘要】：氧是生命活動(dòng)的基本物質(zhì)之一。神經(jīng)系統(tǒng)的氧利用問題更是關(guān)乎機(jī)體健康與否的重要科學(xué)命題。2000年Burmester等首次報(bào)道,腦內(nèi)存在第三種攜氧珠蛋白——腦紅蛋白(NGB),為神經(jīng)系統(tǒng)氧利用的研究帶來新的曙光。為了深入研究NGB與神經(jīng)系統(tǒng)氧利用的關(guān)系,本課題進(jìn)行三方面研究: 首先,采用一系列生物化學(xué)技術(shù)證明了腦紅蛋白與Na~+,K~+-ATPase 1 β2亞基(NKA1b2)之間存在相互作用,在此基礎(chǔ)上提出了全新假說“能量保全可能是神經(jīng)保護(hù)的一個(gè)重要策略”,為神經(jīng)保護(hù)研究領(lǐng)域提供了新觀點(diǎn),并為研發(fā)全新的神經(jīng)保護(hù)藥物用于腦卒中等疾病的治療提供了新的方向。進(jìn)一步,由于目前認(rèn)為腦紅蛋白可能是參與神經(jīng)保護(hù)的一個(gè)重要分子,本文又初步研究了其上游表達(dá)調(diào)控信號(hào)。結(jié)合生物信息學(xué)研究,通過實(shí)驗(yàn)初步顯示P53可能是調(diào)節(jié)腦紅蛋白表達(dá)水平的一個(gè)重要因子。這一研究為剖析以腦紅蛋白為中心的神經(jīng)保護(hù)分子調(diào)控網(wǎng)絡(luò)提供了重要證據(jù)。在對(duì)腦紅蛋白神經(jīng)保護(hù)功能研究的基礎(chǔ)上,為了盡快實(shí)現(xiàn)基礎(chǔ)研究與臨床應(yīng)用之間的對(duì)接,在成功制備抗腦紅蛋白多克隆抗體和單克隆抗體的基礎(chǔ)上,進(jìn)一步研制了具有較高靈敏度的雙抗夾心ELISA檢測(cè)試劑盒并已申報(bào)國(guó)家發(fā)明專利,目前已經(jīng)用于腦缺血損傷與保護(hù)動(dòng)物模型以及臨床上血清標(biāo)本中腦紅蛋白含量的檢測(cè)工作。 綜上所述,本研究揭示了腦紅蛋白神經(jīng)保護(hù)功能的可能機(jī)制,為基于此保護(hù)機(jī)制研發(fā)新的神經(jīng)保護(hù)藥物用于腦卒中的治療奠定了基礎(chǔ),并初步實(shí)現(xiàn)了從基礎(chǔ)研究向臨床應(yīng)用的過渡。在此基礎(chǔ)上,預(yù)期將有可能建立以腦紅蛋白為核心的神經(jīng)損傷與神經(jīng)保護(hù)的理論體系,并將為臨床實(shí)踐中提供全新的神經(jīng)保護(hù)策略提供重要參考價(jià)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.
【學(xué)位授予單位】：中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類號(hào)】：Q593.2

【引證文獻(xiàn)】

相關(guān)期刊論文 前1條

1 尹靜;張祥建;李俐濤;楊q，

本文編號(hào)：2360967