NOD鼠中樞免疫耐受機制異常的研究
發(fā)布時間：2018-11-17 17:59
【摘要】： 自身免疫病主要由于自身耐受(中樞和外周)異常導致。1型糖尿病(T1DM)是其常見疾病之一。但免疫耐受機制如何參與T1DM的發(fā)病仍不清楚。 本實驗以自發(fā)性糖尿病模型鼠-10周齡NOD鼠為研究對象,通過檢測糖尿病相關癥狀及中樞免疫耐受狀態(tài),探討NOD小鼠中樞免疫耐受的缺陷及在自身反應性糖尿病發(fā)生、發(fā)展中的作用。結果顯示: 一.糖尿病相關癥狀NOD小鼠血糖水平與同周齡Balb/c小鼠無明顯差別;尿糖水平均為陰性;自身抗體水平與同齡Balb/c小鼠無明顯差別;NOD小鼠胰島數量減少、分布稀疏、胰島細胞數亦減少同時有大量單核細胞浸潤,表明NOD小鼠出現糖尿病癥狀前已出現了胰島炎。 二.胸腺免疫功能NOD鼠胸腺大小并無明顯萎縮,但病理顯示胸腺皮髓交界不清,髓質細胞減少;胸腺細胞經ConA刺激的應答能力與Balb/c小鼠無明顯差別;胸腺細胞IFN-γ的分泌與Balb/c小鼠無明顯差異,而IL-4的分泌能力明顯低于Balb/c小鼠。 三.中樞免疫耐受狀態(tài)NOD鼠胸腺內insulin表達水平顯著減少,而GAD67和PLP水平沒有顯著變化;胸腺MHC-II類分子的表達水平明顯下降;胸腺內CD4+和CD4+CD25+T細胞水平與同周齡Balb/c小鼠相比無明顯差別。 結論:10周齡NOD小鼠沒有發(fā)生糖尿病,處于前糖尿病階段,但中樞耐受的缺陷可能是最終導致糖尿病發(fā)生的潛在因素。
[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- 緯 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.
【學位授予單位】：吉林大學
【學位級別】：碩士
【學位授予年份】：2007
【分類號】：R392
本文編號：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- 緯 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.
【學位授予單位】：吉林大學
【學位級別】：碩士
【學位授予年份】：2007
【分類號】：R392
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本文編號：2338630
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