低剂量辐射诱导人骨髓间充质干细胞兴奋性及信号机制的体外研究

发布时间：2018-05-26 01:43

本文选题：低剂量辐射 + 骨髓间充质干细胞　；参考：《吉林大学》2007年硕士论文

【摘要】： 1980年,Luckey发现低剂量辐射(LDR)可以刺激细胞的代谢活性,比如DNA和蛋白的合成,他把这种现象叫做兴奋性。到目前为止,整个前期实验表明,暴露在LDR的体内或者体外实验能够提高细胞的代谢活性,包括DNA、RNA和蛋白的合成,DNA的损伤修复、抗氧化活性以及促进骨髓细胞的向外周血的动员等。有关LDR诱导血液系统细胞的生物学反应研究较少,所以LDR在造血系统中的生物学效应并不十分清楚。本研究首次应用体外培养的人源骨髓MSC进行LDR照射,并按照25mGy、75 mGy和200 mGy三种剂量观察照射后4h、24h、48h和72h四个时间点的细胞增殖的变化,发现在众多剂量和时间点中,75mGy照射后24h细胞的增殖是最明显的,而体外K562则不具有上述增殖效应。本研究在观察LDR诱导MSC增殖的信号传导效应方面首次发现LDR是通过P38MAPK途径引起P21、P53表达下降从而介导MSC细胞的增殖反应的,75mGy照射后4h-24h磷酸化P38MAPK表达均上调,其中以12h表达最明显,抑制P38MAPK激酶活性后细胞增殖程度下降,同时P21、P53恢复到对照组水平。本研究首次发现LDR诱导的细胞增殖最佳时间点和诱导细胞磷酸化P38MAPK表达的最佳时间点并不一致,照射后磷酸化P38MAPK表达的高峰期比细胞增殖高峰期要早,这说明LDR是通过P38MAPK信号途径调节细胞核内的相关基因后再引起细胞增殖兴奋性效应的。
[Abstract]:In 1980, Luckey found that low dose radiation (LDR) could stimulate cell metabolic activity, such as the synthesis of DNA and protein, and he called this phenomenon excitability. So far, the whole previous trial showed that exposure to LDR in vivo or in vitro experiments could improve the metabolic activity of cells, including the synthesis of DNA, RNA and protein, and the damage repair of DNA. Complex, antioxidant activity and mobilization of peripheral blood of bone marrow cells, and so on. There are few studies on the biological response of LDR induced blood system cells, so the biological effects of LDR in the hematopoietic system are not very clear.
In this study, LDR irradiation was first used in human bone marrow MSC in vitro, and the proliferation of 4h, 24h, 48h and 72h at four time points were observed at three doses of 25mGy, 75 mGy and 200 mGy. It was found that the proliferation of 24h cells after 75mGy irradiation was the most obvious in many doses and time points, while K562 in vitro did not have the above. Proliferation effect.
In this study, in observing the signal transduction effect of LDR induced MSC proliferation, it was first found that LDR was induced by P38MAPK pathway to induce P21, P53 expression to mediate the proliferation of MSC cells, and 4h-24h phosphorylated P38MAPK expression was up regulation after 75mGy irradiation, and the 12h expression was most obvious, and the proliferation of cells decreased after inhibiting the activity of the P38MAPK kinase activity. At the same time, P21, P53 recovered to the control level.
The best time point of cell proliferation induced by LDR and the best time point for inducing the expression of phosphorylated P38MAPK are not consistent in this study. The peak period of phosphorylated P38MAPK expression after irradiation is earlier than the peak period of cell proliferation, which indicates that LDR is the regulation of the related genes in the nucleus of the fine cell by the P38MAPK signal pathway and then the cell proliferation. Excitatory effects
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R363

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