【摘要】：胸腺是機(jī)體免疫系統(tǒng)的重要組成部分,是T細(xì)胞發(fā)育、分化、成熟的中樞淋巴器官,在免疫系統(tǒng)中發(fā)揮重要的作用。近年來的研究表明胸腺輸出新生T細(xì)胞的能力可持續(xù)終生,在免疫功能重建過程中起著關(guān)鍵性的作用。已知胸腺為電離輻射的高度敏感器官。輻射損傷后,引起的反應(yīng)涉及眾多而復(fù)雜的分子調(diào)控系統(tǒng)。隨著對其反應(yīng)過程復(fù)雜性了解的不斷深入,經(jīng)典的一次僅研究單個或少量基因的生物學(xué)方法已經(jīng)不能滿足現(xiàn)代放射分子生物學(xué)迅速發(fā)展的需要。基因芯片技術(shù)所具有的快速、高效和高通量的突出特點使得其在該領(lǐng)域得到廣泛重視和較快的應(yīng)用。 本實驗應(yīng)用常規(guī)病理形態(tài)學(xué)結(jié)合快速高通量的cDNA基因芯片技術(shù),研究了6.0Gy γ線照射小鼠胸腺組織不同病理階段基因表達(dá)譜的動態(tài)變化,探討胸腺組織輻射損傷與修復(fù)的分了機(jī)制,為研究有效的防治措施提供理論依據(jù)。研究結(jié)果表明: 1、胸腺經(jīng)中等劑量γ射線照射后,經(jīng)歷了淋巴細(xì)胞凋亡和清除期、淋巴細(xì)胞枯竭期、淋巴細(xì)胞再生期、淋巴細(xì)胞早期恢復(fù)期和淋巴細(xì)胞基本恢復(fù)期五個病理發(fā)展階段。 2、不同劑量γ線照射后胸腺淋巴細(xì)胞的凋亡率迅速升高,于24h達(dá)到高峰,在6～12Gy范圍內(nèi)與照射的劑量呈正比,≥15Gy照射后正相關(guān)關(guān)系不明顯。bax、bc1-2、bc1-ⅩL等重要凋亡相關(guān)基因和蛋白在胸腺組織淋巴細(xì)胞凋亡調(diào)控中具有重要作用。 3、胸腺細(xì)胞各亞群對射線的敏感性不同,胸腺功能性細(xì)胞亞群的損傷導(dǎo)致機(jī)體免疫功能的持續(xù)降低并具有潛在的遠(yuǎn)后效應(yīng)。 4、輻射所誘導(dǎo)的胸腺組織差異表達(dá)基因廣泛涉及細(xì)胞周期、免疫和應(yīng)激、細(xì)胞信號轉(zhuǎn)導(dǎo)、轉(zhuǎn)錄調(diào)節(jié)、DNA損傷修復(fù)、細(xì)胞凋亡、細(xì)胞骨架、離子通道和運輸、代謝、蛋白翻譯和合成、發(fā)育、細(xì)胞分化等多個方面。(1)對細(xì)胞周期相關(guān)的基因的分析表明,照射后一部分細(xì)胞發(fā)生了細(xì)胞周期阻滯,另有一部分細(xì)胞繼續(xù)細(xì)胞周期的運轉(zhuǎn)。(2)對信號轉(zhuǎn)導(dǎo)相關(guān)的基因的分析表明,輻射后所激活的信號通路,一方面抑制細(xì)胞的增殖和分化,另一方面產(chǎn)生保護(hù)性信號。(3)對免疫相關(guān)的基因的分析表明,照射后1d
[Abstract]:Thymus is an important part of the immune system and plays an important role in the immune system. It is a central lymphoid organ with T cell development, differentiation and maturity. Recent studies have shown that the ability of thymus to export newborn T cells is sustainable for life and plays a key role in the reconstruction of immune function. The thymus is known to be a highly sensitive organ for ionizing radiation. After radiation damage, the response involves numerous and complex molecular regulatory systems. With the further understanding of the complexity of the reaction process, the classical biological methods which only study a single gene or a few genes at a time can no longer meet the needs of the rapid development of modern radiolecular biology. Because of its rapid, high efficiency and high throughput, gene chip technology has been widely used in this field. In this study, the dynamic changes of gene expression profiles in thymus tissues of mice irradiated with 6.0Gy 緯 rays at different pathological stages were studied by using conventional pathomorphology and rapid high-throughput cDNA gene chip technique. To explore the mechanism of radiation damage and repair of thymus tissue, and to provide theoretical basis for the study of effective prevention and treatment measures. The results showed that: 1. After the thymus were irradiated by medium dose 緯 -rays, the thymus underwent apoptosis and clearance of lymphocytes, depletion of lymphocytes and regeneration of lymphocytes. There are five stages of pathological development in the early recovery period of lymphocytes and the basic recovery stage of lymphocytes. 2. The apoptosis rate of thymus lymphocytes increased rapidly after different doses of 緯 -ray irradiation. The peak was reached at 24 h, which was proportional to the dose of irradiation in the range of 6~12Gy. The positive correlation after irradiation with 鈮，

本文編號：2225766