本文選題：卵巢早衰　切入點(diǎn)：口服耐受　出處：《吉林大學(xué)》2005年博士論文　論文類型：學(xué)位論文

【摘要】：為了探討卵巢早衰(POF)的發(fā)病與自身免疫異常的關(guān)系及開(kāi)發(fā)有效治療POF 的途徑,本試驗(yàn)根據(jù)卵巢透明帶抗原可以誘導(dǎo)自身免疫異常,導(dǎo)致自身免疫性POF 的機(jī)理,合成小鼠透明帶3 的多肽片段(pZP3)。用pZP3 對(duì)小鼠進(jìn)行皮下免疫注射,小鼠出現(xiàn)性周期紊亂、產(chǎn)生抗透明帶抗體、組織形態(tài)學(xué)表現(xiàn)為自身免疫性卵巢炎,表明小鼠發(fā)生POF。本研究克服了以往建立POF 模型方法的缺點(diǎn),為建立POF 動(dòng)物模型提供了一種操作簡(jiǎn)單、發(fā)病率高的方法,有利于對(duì)POF 進(jìn)行臨床診斷學(xué)和治療學(xué)方面的研究�？诜庖咴芍履c道粘膜特異免疫,誘導(dǎo)免疫耐受,即口服耐受。根據(jù)這個(gè)原理,本研究嘗試用口服耐受來(lái)治療自身免疫性POF,用pZP3給小鼠灌胃,同時(shí)給小鼠進(jìn)行皮下免疫注射pZP3,與對(duì)照組相比,中劑量及大劑量治療組小鼠呈現(xiàn)規(guī)律的性周期、外周血中的CD25+CD4+T 細(xì)胞數(shù)量明顯增加、外周血及卵巢中的抗透明帶抗體陽(yáng)性率均明顯降低、且無(wú)自身免疫性卵巢炎的表現(xiàn),因此,口服pZP3 可以抑制自身免疫性POF的發(fā)病,為治療POF 開(kāi)辟了一條新的道路。另外,本實(shí)驗(yàn)還檢測(cè)了人類POF 患者外周血中的抗透明帶抗體的表達(dá)及Th1、Th2 型細(xì)胞因子的水平,證實(shí)了自身免疫異常是導(dǎo)致POF 發(fā)病的一個(gè)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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2005
【分類號(hào)】：R-332;R711.7

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