NOD鼠中枢免疫耐受机制异常的研究
发布时间：2018-11-17 17:59
【摘要】： 自身免疫病主要由于自身耐受(中枢和外周)异常导致。1型糖尿病(T1DM)是其常见疾病之一。但免疫耐受机制如何参与T1DM的发病仍不清楚。 本实验以自发性糖尿病模型鼠-10周龄NOD鼠为研究对象,通过检测糖尿病相关症状及中枢免疫耐受状态,探讨NOD小鼠中枢免疫耐受的缺陷及在自身反应性糖尿病发生、发展中的作用。结果显示: 一.糖尿病相关症状NOD小鼠血糖水平与同周龄Balb/c小鼠无明显差别;尿糖水平均为阴性;自身抗体水平与同龄Balb/c小鼠无明显差别;NOD小鼠胰岛数量减少、分布稀疏、胰岛细胞数亦减少同时有大量单核细胞浸润,表明NOD小鼠出现糖尿病症状前已出现了胰岛炎。 二.胸腺免疫功能NOD鼠胸腺大小并无明显萎缩,但病理显示胸腺皮髓交界不清,髓质细胞减少;胸腺细胞经ConA刺激的应答能力与Balb/c小鼠无明显差别;胸腺细胞IFN-γ的分泌与Balb/c小鼠无明显差异,而IL-4的分泌能力明显低于Balb/c小鼠。 三.中枢免疫耐受状态NOD鼠胸腺内insulin表达水平显著减少,而GAD67和PLP水平没有显著变化;胸腺MHC-II类分子的表达水平明显下降;胸腺内CD4+和CD4+CD25+T细胞水平与同周龄Balb/c小鼠相比无明显差别。 结论:10周龄NOD小鼠没有发生糖尿病,处于前糖尿病阶段,但中枢耐受的缺陷可能是最终导致糖尿病发生的潜在因素。
[Abstract]:Autoimmune disease is mainly caused by abnormal autotolerance (central and peripheral). Type 1 diabetes mellitus (T1DM) is one of its common diseases. However, the mechanism of immune tolerance involved in the pathogenesis of T1DM remains unclear. In this study, NOD mice aged from 10 weeks to 10 weeks old with spontaneous diabetes mellitus were used to investigate the deficiency of central immune tolerance and the occurrence of autoreactive diabetes mellitus in NOD mice by detecting the symptoms related to diabetes and the state of central immune tolerance. The role of development The results show that: 1. There was no significant difference in blood glucose level between NOD mice and Balb/c mice of the same age, urine glucose level was negative, there was no significant difference between autoantibodies and Balb/c mice of the same age. The number and distribution of islets in NOD mice decreased and the number of islet cells decreased and a large number of monocytes infiltrated indicating that islet inflammation had occurred in NOD mice before the onset of diabetic symptoms. II. The thymus size of NOD mice with thymus immune function did not atrophy, but pathology showed that the border of thymic dermis was unclear and the medullary cells decreased, and the response ability of thymocytes stimulated by ConA was not significantly different from that of Balb/c mice. There was no significant difference in the secretion of IFN- 纬 between thymocytes and Balb/c mice, but the secretory ability of IL-4 was significantly lower than that of Balb/c mice. Three The expression of insulin in thymus of NOD rats was significantly decreased, but GAD67 and PLP levels were not significantly changed, and the expression level of MHC-II molecules in thymus was significantly decreased. The levels of CD4 and CD4 CD25 T cells in thymus were not significantly different from those of Balb/c mice at the same age. Conclusion: NOD mice at 10 weeks of age did not develop diabetes and were in the stage of prediabetes, but the deficiency of central tolerance may be the potential factor leading to the development of diabetes.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R392
本文编号：2338630
[Abstract]:Autoimmune disease is mainly caused by abnormal autotolerance (central and peripheral). Type 1 diabetes mellitus (T1DM) is one of its common diseases. However, the mechanism of immune tolerance involved in the pathogenesis of T1DM remains unclear. In this study, NOD mice aged from 10 weeks to 10 weeks old with spontaneous diabetes mellitus were used to investigate the deficiency of central immune tolerance and the occurrence of autoreactive diabetes mellitus in NOD mice by detecting the symptoms related to diabetes and the state of central immune tolerance. The role of development The results show that: 1. There was no significant difference in blood glucose level between NOD mice and Balb/c mice of the same age, urine glucose level was negative, there was no significant difference between autoantibodies and Balb/c mice of the same age. The number and distribution of islets in NOD mice decreased and the number of islet cells decreased and a large number of monocytes infiltrated indicating that islet inflammation had occurred in NOD mice before the onset of diabetic symptoms. II. The thymus size of NOD mice with thymus immune function did not atrophy, but pathology showed that the border of thymic dermis was unclear and the medullary cells decreased, and the response ability of thymocytes stimulated by ConA was not significantly different from that of Balb/c mice. There was no significant difference in the secretion of IFN- 纬 between thymocytes and Balb/c mice, but the secretory ability of IL-4 was significantly lower than that of Balb/c mice. Three The expression of insulin in thymus of NOD rats was significantly decreased, but GAD67 and PLP levels were not significantly changed, and the expression level of MHC-II molecules in thymus was significantly decreased. The levels of CD4 and CD4 CD25 T cells in thymus were not significantly different from those of Balb/c mice at the same age. Conclusion: NOD mice at 10 weeks of age did not develop diabetes and were in the stage of prediabetes, but the deficiency of central tolerance may be the potential factor leading to the development of diabetes.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R392
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