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甲状腺相关眼病动物模型建立及发病机理研究

发布时间:2019-01-11 15:07
【摘要】:目的: TAO是眼科临床常见眼眶病病因之一,患病率在眼眶疾病中居首位。目前认为,TAO是由于自身免疫反应影响到眶周及球后组织,以淋巴细胞浸润为特点伴有粘多糖及胶原沉积,以水肿、突眼和复视为临床表现的一种器官特异性自身免疫性疾病。对TAO的研究要么是缺乏可复制的动物模型,要么就是在疾病的早期难以获得眼眶组织,致其具体病因及确切的发病机制仍不完全明了。因此,要详细了解TAO各方面的改变,探寻有效防治措施,就在于要建立适当的动物模型。 目前国外多采用的TAO建模方法是用TSHR多肽或核酸免疫、TSHR转染细胞或TSHR活化T细胞免疫和多基因联合免疫等。比较理想的方法是TSHR活化细胞或TSHR基因免疫方法。 本研究旨在探讨TSHR基因免疫方法构建TAO动物模型,,观察免疫后的TAO模型动物眼眶组织和甲状腺的组织病理学变化以及眼眶组织Th1/Th2免疫反应类型;同时研究IL-4与IFN-γ干预后TAO模型动物眼眶组织和甲状腺组织病理学变化以及眼眶组织Th1/Th2免疫反应平衡的改变,为进一步探讨TAO发病机制以及临床防治奠定理论基础。 方法: 本研究分为三个部分。
[Abstract]:Objective: TAO is one of the common causes of orbital diseases in ophthalmology. It is believed that TAO is an organ-specific autoimmune disease characterized by lymphocytic infiltration accompanied by mucopolysaccharide and collagen deposition, edema, exophthalmos and recombination as clinical manifestations due to the autoimmune effects of autoimmune responses to periorbital and retrobulbar tissues. The study of TAO is either lack of replicable animal models or it is difficult to obtain orbital tissue at the early stage of the disease. Therefore, it is necessary to establish appropriate animal models to understand the changes of TAO in detail and to explore effective prevention and treatment measures. At present, most TAO modeling methods are immunized with TSHR polypeptide or nucleic acid, TSHR transfected cells or TSHR activated T cell immunity and multi-gene combined immunity. The ideal method is TSHR activated cell or TSHR gene immunization. The purpose of this study was to investigate the establishment of TAO animal model by TSHR gene immunization and to observe the histopathological changes of orbital and thyroid tissues and the types of Th1/Th2 immunoreaction in orbital tissues of TAO model animals after immunization. At the same time, the pathological changes of orbital and thyroid tissues and the changes of Th1/Th2 immunoreaction balance in orbital tissues of TAO model rats after intervention with IL-4 and IFN- 纬 were studied, which laid a theoretical foundation for the further study of the pathogenesis of TAO and the clinical prevention and treatment. Methods: the study was divided into three parts.
【学位授予单位】:四川大学
【学位级别】:博士
【学位授予年份】:2006
【分类号】:R-332;R771.3

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