胸腺组织辐射损伤效应和机理的研究
发布时间：2018-09-06 08:18
【摘要】：胸腺是机体免疫系统的重要组成部分,是T细胞发育、分化、成熟的中枢淋巴器官,在免疫系统中发挥重要的作用。近年来的研究表明胸腺输出新生T细胞的能力可持续终生,在免疫功能重建过程中起着关键性的作用。已知胸腺为电离辐射的高度敏感器官。辐射损伤后,引起的反应涉及众多而复杂的分子调控系统。随着对其反应过程复杂性了解的不断深入,经典的一次仅研究单个或少量基因的生物学方法已经不能满足现代放射分子生物学迅速发展的需要。基因芯片技术所具有的快速、高效和高通量的突出特点使得其在该领域得到广泛重视和较快的应用。 本实验应用常规病理形态学结合快速高通量的cDNA基因芯片技术,研究了6.0Gy γ线照射小鼠胸腺组织不同病理阶段基因表达谱的动态变化,探讨胸腺组织辐射损伤与修复的分了机制,为研究有效的防治措施提供理论依据。研究结果表明: 1、胸腺经中等剂量γ射线照射后,经历了淋巴细胞凋亡和清除期、淋巴细胞枯竭期、淋巴细胞再生期、淋巴细胞早期恢复期和淋巴细胞基本恢复期五个病理发展阶段。 2、不同剂量γ线照射后胸腺淋巴细胞的凋亡率迅速升高,于24h达到高峰,在6～12Gy范围内与照射的剂量呈正比,≥15Gy照射后正相关关系不明显。bax、bc1-2、bc1-ⅩL等重要凋亡相关基因和蛋白在胸腺组织淋巴细胞凋亡调控中具有重要作用。 3、胸腺细胞各亚群对射线的敏感性不同,胸腺功能性细胞亚群的损伤导致机体免疫功能的持续降低并具有潜在的远后效应。 4、辐射所诱导的胸腺组织差异表达基因广泛涉及细胞周期、免疫和应激、细胞信号转导、转录调节、DNA损伤修复、细胞凋亡、细胞骨架、离子通道和运输、代谢、蛋白翻译和合成、发育、细胞分化等多个方面。(1)对细胞周期相关的基因的分析表明,照射后一部分细胞发生了细胞周期阻滞,另有一部分细胞继续细胞周期的运转。(2)对信号转导相关的基因的分析表明,辐射后所激活的信号通路,一方面抑制细胞的增殖和分化,另一方面产生保护性信号。(3)对免疫相关的基因的分析表明,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 纬 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 纬 -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 纬 -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，
本文编号：2225766
[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 纬 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 纬 -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 纬 -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，
本文编号：2225766
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