【摘要】：白細胞介素超家族和谷胱甘肽過氧化物酶是重要的細胞因子，在研究中我們發(fā)現(xiàn)白介素1受體拮抗劑(sIL1rn)和谷胱甘肽過氧化物酶(Gpx7)在造血干細胞(HSCs)擴增中具有正調(diào)節(jié)因子的作用，能夠有效促進HSCs的擴增。 首先我們通過注射5—氟尿嘧啶(5-FU)建立了小鼠造血應(yīng)急反應(yīng)模型，展示了骨髓抑制和再生過程。并運用基因芯片分析方法，，對此模型中第0、3、7、11、14天的基因表達差異進行比較研究，獲得了小鼠骨髓抑制和再生的基因表達圖譜。根據(jù)這個圖譜，我們發(fā)現(xiàn)了一組在此過程中表現(xiàn)出與造血調(diào)節(jié)功能明顯相關(guān)的細胞因子基因。本文對其中的兩個基因—sIL1rn和Gpx7基因進行了克隆。將sIL1rn接入真核表達載體phCMV，同時將Gpx7接入真核表達載體pcDNA3.1，并通過肌肉注射、電擊穿孔、體內(nèi)表達等方法獲得了該基因在小鼠脛前肌的高效表達，初步研究了sIL1rn和Gpx7在骨髓造血過程中的功能。結(jié)果表明，體內(nèi)表達sIL1rn能顯著增加5-FU注射后小鼠外周血白細胞數(shù)，能將骨髓抑制時間由14天縮短到11天左右。Gpx7可以明顯增加骨髓細胞恢復(fù)數(shù)量。同時，對基因芯片發(fā)現(xiàn)的與sIL1rn具有一定協(xié)同作用的生長激素，利用皮下注射融合蛋白的方法，也進行了初步的功能研究。
[Abstract]:Interleukin-superfamily and glutathione peroxidase are important cytokines. We found that interleukin-1 receptor antagonists (sIL1rn) and glutathione peroxidase (Gpx7) play a positive role in the (HSCs) amplification of hematopoietic stem cells and can effectively promote the expansion of HSCs. First, we established a mouse hematopoietic emergency response model by injecting 5-fluorouracil (5-FU) to demonstrate the process of bone marrow suppression and regeneration. Using the method of gene chip analysis, the difference of gene expression in the model was studied on day 71114, and the gene expression map of bone marrow suppression and regeneration in mice was obtained. Based on this map, we found a set of cytokine genes that were significantly associated with hematopoietic regulation. In this paper, two genes, sIL1rn and Gpx7, were cloned. SIL1rn was inserted into the eukaryotic expression vector phCMV, and Gpx7 was inserted into the eukaryotic expression vector pcDNA3.1,. The gene was expressed in the anterior tibial muscle of mice by intramuscular injection, electroporation and in vivo expression. The function of sIL1rn and Gpx7 in bone marrow hematopoiesis was studied. The results showed that the expression of sIL1rn in vivo could significantly increase the number of leukocytes in peripheral blood of mice injected with 5-FU and shorten the time of bone marrow suppression from 14 days to about 11 days. Gpx7 could significantly increase the number of bone marrow cells recovered. At the same time, the function of growth hormone with sIL1rn was studied by subcutaneous injection of fusion protein.
【學(xué)位授予單位】：沈陽藥科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2006
【分類號】：R346

【參考文獻】

相關(guān)期刊論文 前1條

1 郭甫坤,吳曙光;白介素1信號轉(zhuǎn)導(dǎo)研究進展[J];國外醫(yī)學(xué).分子生物學(xué)分冊;2001年01期

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