PCOS大鼠模型的建立及盐酸吡咯列酮对PCOS大鼠下丘脑及卵巢中瘦素受体表达的影响

发布时间：2018-01-01 08:07

本文关键词：PCOS大鼠模型的建立及盐酸吡咯列酮对PCOS大鼠下丘脑及卵巢中瘦素受体表达的影响　出处：《福建医科大学》2008年硕士论文　论文类型：学位论文

【摘要】： 【目的】评价来曲唑诱导多囊卵巢综合征(Polysystic Ovary Syndrome,PCOS)大鼠模型的意义,分析瘦素受体(leptin receptor,Lep R)与PCOS的关系,研究盐酸吡咯列酮对PCOS大鼠下丘脑和卵巢中Lep R的影响。【方法】将30只雌性SD大鼠分为三组:正常对照组、PCOS组、盐酸吡咯列酮干预组。测定各组大鼠血清T、LH、FG、INS、LEP水平,通过免疫组织化学、Real Time RT PCR方法检测各组大鼠下丘脑、卵巢中Lep R的相对表达。【结果】1.来曲唑诱导PCOS大鼠模型,符合PCOS的内分泌特征,具备高胰岛素血症和高瘦素血症。2. PCOS大鼠经盐酸吡咯列酮干预后血清T、LH、INS、LEP明显下降(P 0.05)。相关分析得出:T与HOMA-IR、INS均呈正相关(rs=0.443,0.366;P 0.05)。3.经免疫组织化学、Real Time RT PCR方法相对定量检测各组下丘脑、卵巢中Lep R的表达,提示PCOS大鼠下丘脑Lep R表达较正常对照组减弱(P 0.05),盐酸吡咯列酮干预后下丘脑Lep R表达增强(P 0.05)。而卵巢中Lep R表达与下丘脑正好相反,即PCOS大鼠卵巢中Lep R表达较正常对照组增强(P 0.05),经盐酸吡咯列酮干预后卵巢Lep R表达减弱(P 0.05)。【结论】1.来曲唑诱导PCOS大鼠模型是目前研究PCOS发病机制,胰岛素抵抗、瘦素抵抗的发生机制较合适的建立方法。2. PCOS大鼠下丘脑Lep R表达减低导致瘦素抵抗,可能是PCOS产生无排卵、月经紊乱等内分泌紊乱的主要原因。PCOS大鼠卵巢中Lep R表达增强,导致瘦素的生理作用增强,即增强了瘦素对卵巢分泌雌、孕激素功能的抑制作用,可能是PCOS大鼠不排卵,生育力下降的原因。3.胰岛素增敏剂—盐酸吡咯列酮改善PCOS大鼠高胰岛素血症、高瘦素血症、高雄激素血症等内分泌异常的同时使PCOS大鼠下丘脑Lep R表达增强,有效改善了瘦素抵抗;同时卵巢LepR表达下调,减弱了瘦素对卵巢分泌雌、孕激素功能的抑制作用,改善卵巢性激素分泌的功能。
[Abstract]:[objective] to evaluate the significance of letrozole induced polycystic Ovary Syndromes (PCOS) rat model. To study the effect of pyrrolidone hydrochloride on Lep in hypothalamus and ovary of PCOS rats by analyzing the relationship between leptin receptor leptin receptor Lep R) and PCOS. The influence of R. [methods] Thirty female Sprague-Dawley rats were divided into three groups: normal control group, PCOS group and pyrrolidone hydrochloride intervention group. The relative expression of Lep R in hypothalamus and ovary was detected by real Time RT PCR method. [results] 1. Letrozole induced PCOS rat model, according to the endocrine characteristics of PCOS. 2. The rats with hyperinsulinemia and hyperleptinemia. 2. PCOS rats were treated with pyrrolidone hydrochloride. LEP decreased significantly (P 0.05). Correlation analysis showed that there was a positive correlation between LEP and HOMA-IRINS. The expression of Lep R in hypothalamus and ovary was detected by real Time RT PCR method. The results suggest that the expression of Lep R in hypothalamus of PCOS rats is lower than that of normal control group (P 0.05). The expression of Lep R in hypothalamus increased after the intervention of pyrrolidone hydrochloride, but the expression of Lep R in ovary was opposite to that in hypothalamus. The expression of Lep R in the ovary of PCOS rats was significantly higher than that of the normal control group (P 0.05), and the expression of Lep R in the ovary was decreased after the intervention of pyrrolidone hydrochloride. [conclusion] 1.The rat model of PCOS induced by letrozole is the current study of the pathogenesis of PCOS, insulin resistance. 2. The mechanism of leptin resistance is more suitable to establish method .2.The decrease of Lep R expression in hypothalamus of PCOS rats may lead to leptin resistance, which may be caused by PCOS anovulation. The main reason of endocrine disorder, such as menstrual disorder, is that the expression of Lep R in the ovary of PCOS rats is increased, which leads to the enhancement of the physiological function of leptin, that is, it enhances the secretion of leptin to the ovary. The inhibition of progesterone function may be the reason for the decline of fertility and anovulation in PCOS rats. 3. The insulin sensitizer, pyrrolidone hydrochloride, can improve hyperinsulinemia and hyperleptinemia in PCOS rats. The endocrine abnormalities such as hyperandrogenemia increased the expression of Lep R in hypothalamus of PCOS rats and effectively improved leptin resistance. At the same time, the expression of LepR in the ovary was down-regulated, which weakened the inhibitory effect of leptin on the secretion of estrogen and progesterone, and improved the function of the secretion of ovarian sex hormone.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R711.75;R-332

【参考文献】