卵巢早衰动物模型的建立及口服耐受治疗自身免疫性卵巢早衰的相关研究

发布时间：2018-03-17 01:14

本文选题：卵巢早衰　切入点：口服耐受　出处：《吉林大学》2005年博士论文　论文类型：学位论文

【摘要】：为了探讨卵巢早衰(POF)的发病与自身免疫异常的关系及开发有效治疗POF 的途径,本试验根据卵巢透明带抗原可以诱导自身免疫异常,导致自身免疫性POF 的机理,合成小鼠透明带3 的多肽片段(pZP3)。用pZP3 对小鼠进行皮下免疫注射,小鼠出现性周期紊乱、产生抗透明带抗体、组织形态学表现为自身免疫性卵巢炎,表明小鼠发生POF。本研究克服了以往建立POF 模型方法的缺点,为建立POF 动物模型提供了一种操作简单、发病率高的方法,有利于对POF 进行临床诊断学和治疗学方面的研究。口服免疫原可致肠道粘膜特异免疫,诱导免疫耐受,即口服耐受。根据这个原理,本研究尝试用口服耐受来治疗自身免疫性POF,用pZP3给小鼠灌胃,同时给小鼠进行皮下免疫注射pZP3,与对照组相比,中剂量及大剂量治疗组小鼠呈现规律的性周期、外周血中的CD25+CD4+T 细胞数量明显增加、外周血及卵巢中的抗透明带抗体阳性率均明显降低、且无自身免疫性卵巢炎的表现,因此,口服pZP3 可以抑制自身免疫性POF的发病,为治疗POF 开辟了一条新的道路。另外,本实验还检测了人类POF 患者外周血中的抗透明带抗体的表达及Th1、Th2 型细胞因子的水平,证实了自身免疫异常是导致POF 发病的一个重要因素。
[Abstract]:In order to investigate the relationship between the pathogenesis of premature ovarian failure (POF) and autoimmune abnormality and to develop an effective approach for the treatment of POF, the mechanism of autoimmune POF can be induced by ovarian pellucida antigen. The polypeptide fragment pZP3 of mouse pZP3 was synthesized. Subcutaneously immunized mice were injected with pZP3. The sexual cycle was disorder and anti-pellucida antibody was produced in mice. The histomorphology showed autoimmune ovaritis. This study overcomes the shortcomings of the previous methods of establishing POF model and provides a simple and high incidence method for the establishment of POF animal model. It is beneficial to the clinical diagnosis and therapeutics of POF. Oral immunogen can induce intestinal mucosal specific immunity and induce immune tolerance, that is, oral tolerance. In this study, oral tolerance was used to treat autoimmune POFs, pZP3 was given to mice and subcutaneous immunized mice were injected with pZP3. Compared with the control group, the mice in the middle and high dose groups showed regular sexual cycle. The number of CD25 CD4 T cells in peripheral blood was significantly increased, and the positive rate of anti-pellucida antibody in peripheral blood and ovary was significantly decreased, and there was no autoimmune ovaritis. Therefore, oral pZP3 could inhibit the pathogenesis of autoimmune POF. In addition, the expression of anti-pellucida antibody and the level of Th1Th _ 2 cytokines in peripheral blood of patients with POF were detected, which confirmed that autoimmune abnormality was an important factor leading to the pathogenesis of POF.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R-332;R711.7

【共引文献】