自身免疫性糖尿病模型鼠免疫耐受机制异常的研究
发布时间：2019-05-13 13:57
【摘要】：自身免疫耐受是指免疫系统对自身抗原的特异性免疫无反应状态,是维持免疫自稳的重要机制。自身耐受主要是通过中枢耐受和外周耐受两大机制来维持。为了进一步揭示机体自身免疫耐受在维持自身稳定、调节免疫平衡、防止自身免疫病中的作用,本文分别应用多次低剂量STZ注射诱导的糖尿病(MLDS-DM)模型和自发1型糖尿病(T1DM)的NOD小鼠,在疾病的不同发展阶段,全面系统地探讨了自身免疫耐受机制异常在自身免疫性糖尿病发生中的作用。 一、STZ诱导的糖尿病模型 首先,为了探讨不同剂量STZ诱导糖尿病模型的机制,寻找STZ诱导1型糖尿病模型的最佳剂量及T1DM发生的免疫应答特点。检测了糖尿病模型的相关指标及细胞和体液免疫功能。在此基础上,为了研究糖尿病模型中枢和外周耐受异常是STZ直接作用还是间接作用的结果,本实验采用在STZ诱导糖尿病模型同时补充胰岛素,以探讨STZ诱导的糖尿病模型中枢和外周免疫耐受异常的机制。 结果表明: 1.小剂量STZ(20 mg/kg·bw)和中等剂量STZ(40 mg/kg·bw)诱导产生细胞和体液免疫应答参与的自身免疫性糖尿病(T1DM),但以40 mg/kg·bw STZ诱导的T1DM的效果最佳;而大剂量STZ(80mg/kg·bw)直接破坏胰岛β细胞,诱导小鼠产生II型糖尿病。 2.STZ以某种机制直接作用于胸腺,影响了T细胞在胸腺内的选择、分化,导致中枢耐受异常,从而引起T1DM的发生。另外,STZ直接破坏胰岛β细胞,胰岛素分泌水平降低,造成胸腺细胞的营养障碍,间接损伤胸腺的结构和功能,进一步打破了中枢耐受机制,促进了自身免疫病的发展。
[Abstract]:Autoimmune tolerance refers to the specific immune response of the immune system to autoantigens, and is an important mechanism to maintain immune homeostasis. Self-tolerance is mainly maintained through central tolerance and peripheral tolerance. In order to further reveal the role of autoimmune tolerance in maintaining self-stability, regulating immune balance and preventing autoimmune diseases, The diabetic (MLDS-DM) model induced by multiple low dose STZ injection and NOD mice with spontaneous type 1 diabetes mellitus (T1DM) were used at different stages of disease development. The role of abnormal mechanism of autoimmune tolerance in the occurrence of autoimmune diabetes mellitus was discussed comprehensively and systematically. First of all, in order to explore the mechanism of diabetes induced by different doses of STZ, the best dose of STZ induced type 1 diabetes model and the immune response characteristics of T1DM were found in the diabetic model induced by STZ. The related indexes and cellular and humoral immune function of diabetic model were detected. On this basis, in order to study whether the abnormal central and peripheral tolerance of diabetic model was the direct or indirect effect of STZ, insulin was supplemented in STZ induced diabetic model at the same time. To investigate the mechanism of abnormal central and peripheral immune tolerance in diabetic model induced by STZ. The results show that: 1. Low dose STZ (20 mg/ kg 路bw) and medium dose STZ (40 mg/ kg 路bw) induced autoimmune diabetes mellitus (T1DM) with cellular and humoral immune responses, but 40 mg/ kg 路bw STZ induced T1DM was the best. High dose STZ (80mg/ kg 路bw) directly destroyed islet 尾 cells and induced type II diabetes in mice. 2.STZ acts directly on the thymic gland by some mechanism, which affects the selection and differentiation of T cells in the thymic gland, and leads to abnormal central tolerance, which leads to the occurrence of T1DM. In addition, STZ directly destroys islet 尾 cells, reduces insulin secretion, causes nutritional disorders of thymocytes, indirectly damages the structure and function of thymocytes, further breaks the mechanism of central tolerance and promotes the development of autoimmune diseases.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392;R587.1
本文编号：2475941
[Abstract]:Autoimmune tolerance refers to the specific immune response of the immune system to autoantigens, and is an important mechanism to maintain immune homeostasis. Self-tolerance is mainly maintained through central tolerance and peripheral tolerance. In order to further reveal the role of autoimmune tolerance in maintaining self-stability, regulating immune balance and preventing autoimmune diseases, The diabetic (MLDS-DM) model induced by multiple low dose STZ injection and NOD mice with spontaneous type 1 diabetes mellitus (T1DM) were used at different stages of disease development. The role of abnormal mechanism of autoimmune tolerance in the occurrence of autoimmune diabetes mellitus was discussed comprehensively and systematically. First of all, in order to explore the mechanism of diabetes induced by different doses of STZ, the best dose of STZ induced type 1 diabetes model and the immune response characteristics of T1DM were found in the diabetic model induced by STZ. The related indexes and cellular and humoral immune function of diabetic model were detected. On this basis, in order to study whether the abnormal central and peripheral tolerance of diabetic model was the direct or indirect effect of STZ, insulin was supplemented in STZ induced diabetic model at the same time. To investigate the mechanism of abnormal central and peripheral immune tolerance in diabetic model induced by STZ. The results show that: 1. Low dose STZ (20 mg/ kg 路bw) and medium dose STZ (40 mg/ kg 路bw) induced autoimmune diabetes mellitus (T1DM) with cellular and humoral immune responses, but 40 mg/ kg 路bw STZ induced T1DM was the best. High dose STZ (80mg/ kg 路bw) directly destroyed islet 尾 cells and induced type II diabetes in mice. 2.STZ acts directly on the thymic gland by some mechanism, which affects the selection and differentiation of T cells in the thymic gland, and leads to abnormal central tolerance, which leads to the occurrence of T1DM. In addition, STZ directly destroys islet 尾 cells, reduces insulin secretion, causes nutritional disorders of thymocytes, indirectly damages the structure and function of thymocytes, further breaks the mechanism of central tolerance and promotes the development of autoimmune diseases.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392;R587.1
【参考文献】
相关期刊论文 前1条
1 孙子林,葛祖恺;糖尿病动物模型及其进展[J];中国糖尿病杂志;1999年04期
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