發(fā)布時間：2018-03-18 11:00

  本文選題：酸性　切入點：纖維　出處：《吉林大學》2005年博士論文　論文類型：學位論文

【摘要】：酸性成纖維細胞生長因子(aFGF)在機體生長發(fā)育中發(fā)揮重要的有絲分裂作用。aFGF還具有非促分裂作用,如神經保護和心肌缺血保護等。aFGF在體外發(fā)揮非促分裂作用時,可能會產生由促分裂活性誘導的細胞轉化,從而有引起細胞非正常增殖而可能產生的潛在危險。 為了研究降低aFGF促分裂活性方法,從研究aFGF多肽鏈上的核轉位序列與aFGF的信號途徑的關聯(lián)入手。通過人工敲除aFGF的該序列,制備了重組aFGF蛋白凍干粉(raFGF)。檢測了兩種蛋白的有絲分裂活性和受體酪氨酸激酶的信號途徑。經比較分析認為,rFGF的促分裂活性明顯低于waFGF。分析表明,raFGF的促分裂活性只與MAPK的級聯(lián)有關,而不能夠通過核轉位途徑發(fā)揮作用,而核轉位序列在核轉位途徑中發(fā)揮重要作用。waFGF則可通過兩種途徑的協(xié)同作用發(fā)揮促分裂活性。對raFGF的細胞效應檢測表明,raFGF具有維持細胞正常生存、避免發(fā)生細胞凋亡的作用。該研究結果在我們所做的動物實驗中進一步得到的補充,即raFGF不但能夠延長aFGF缺乏的新生大鼠的生存時間,而且還能夠在一定程度上具有維持幼鼠正常神經系統(tǒng)功能的作用。而重要信號途徑的喪失則有可能使raFGF的誘發(fā)細胞轉化的可能性極小。
[Abstract]:Acidic fibroblast growth factor (aFGF) plays an important mitotic role in the growth and development of the body. AFGF also has non-mitogenic effects, such as neuroprotection and myocardial ischemia protection. Cell transformation may be induced by mitogenic activity, which may lead to abnormal cell proliferation. In order to study the method of reducing the mitogenic activity of aFGF, the correlation between the nuclear translocation sequence on aFGF polypeptide chain and the signal pathway of aFGF was studied. The recombinant aFGF protein freeze-dried powder was prepared. The mitotic activity and signal pathway of receptor tyrosine kinase of two proteins were detected. The results showed that the mitogenic activity of rFGF was significantly lower than that of waFGF. The results showed that the mitogenic activity of the two proteins was significantly lower than that of Waff FGF.The results showed that the mitogenic activity of the two proteins was significantly lower than that of Waff FGF. Only related to the cascades of MAPK, But not through nuclear translocation, The nuclear translocation sequence plays an important role in the nuclear translocation pathway. WaFGF can play a mitogenic role through the synergistic action of the two pathways. The detection of the cellular effect of raFGF shows that it can maintain the normal survival of the cells. The effect of cell apoptosis. The results of this study are further supplemented by our animal experiments, that is, raFGF can not only prolong the survival time of newborn rats lacking aFGF. Moreover, it can maintain the normal nervous system function of young rats to some extent, and the loss of important signal pathway may make the possibility of cell transformation induced by raFGF very small.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2005
【分類號】：R329

【共引文獻】

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