發(fā)布時(shí)間：2018-03-12 17:22

  本文選題：leptin　切入點(diǎn)：神經(jīng)肽Y　出處：《河北醫(yī)科大學(xué)》2005年博士論文　論文類(lèi)型：學(xué)位論文

【摘要】：1994 年,Zhang 等學(xué)者利用定位克隆技術(shù)成功克隆了小鼠的肥胖基因(obese gene, ob )及人類(lèi)的同源序列,ob 基因編碼的蛋白質(zhì)產(chǎn)物被稱(chēng)為leptin,譯為瘦素。leptin 的發(fā)現(xiàn)使脂肪量和某些中樞部位可能存在著一定信號(hào)聯(lián)系參與調(diào)節(jié)能量平衡和生殖這一存在了40 多年的假說(shuō)得以證實(shí)。ob/ob 鼠和db/db(diabete gene, db)鼠分別由于leptin 基因突變和leptin 受體的基因突變而具有相似的表現(xiàn):嚴(yán)重的早發(fā)肥胖,嚴(yán)重的胰島素抵抗,飲食過(guò)多,能耗降低,不孕不育。但是,給予ob/ob 鼠腹腔注射leptin 后,不僅體重和攝食恢復(fù)至正常水平,生育能力也得以糾正;在雌性ob/ob 鼠卵巢和子宮的重量增加,血清黃體生成素(luteinizing hormone,LH)濃度增加,原始卵泡和囊狀卵泡數(shù)量增多;在雄性ob/ob 鼠睪丸和精囊腺重量增加,生成精子數(shù)量增多。這些實(shí)驗(yàn)結(jié)果說(shuō)明leptin 在調(diào)節(jié)攝食與能量消耗的同時(shí)也參與了對(duì)生殖功能的調(diào)控。 盡管有大量的證據(jù)支持leptin 調(diào)節(jié)生殖功能的角色,然而leptin 究竟是直接還是間接調(diào)節(jié)下丘腦-垂體-性腺軸,仍舊需要更多的工作去闡明。因此,本實(shí)驗(yàn)研究leptin 對(duì)生殖軸中下丘腦的可能作用,期望通過(guò)觀察leptin 對(duì)下丘腦神經(jīng)肽Y 神經(jīng)元(Neuropeptide Y, NPY)表達(dá)的影響,能夠初步探討leptin 調(diào)控生殖的可能作用機(jī)理,為leptin 的臨床應(yīng)用提供一定的實(shí)驗(yàn)依據(jù)。研究?jī)?nèi)容與結(jié)果如下: 一、obR 與NPY 在小鼠下丘腦的共表達(dá) 目的:leptin 是連接營(yíng)養(yǎng)與生殖的代謝信號(hào),在生殖軸中發(fā)揮重要作用。由于未能發(fā)現(xiàn)obR 和obRmRNA 與GnRH 神經(jīng)元在中樞的共性表達(dá),大多數(shù)學(xué)者認(rèn)為leptin 是間接作用于GnRH 神經(jīng)元影響其分泌,而NPY 是目前研究最多的參與能量平衡和神經(jīng)內(nèi)分泌調(diào)控的重要調(diào)質(zhì),推測(cè)NPY可能介導(dǎo)了leptin 和GnRH 神經(jīng)元之間的調(diào)節(jié)作用。所以實(shí)驗(yàn)中我們首先觀察obR 與NPY 在小鼠下丘腦的分布,然后進(jìn)一步觀察兩者在下丘腦的是否有共存情況,并以此作為下一步實(shí)驗(yàn)設(shè)計(jì)的依據(jù)。方法:選用成年雌性C57bl/6J 小鼠,經(jīng)左心室用生理鹽水和4%多聚
[Abstract]:In 1994, Zhang and other researchers successfully cloned the mouse obesity gene (ob) and the protein product encoded by the homologous sequence of human gene (ob) by using the technique of location-cloning. The discovery of leptin, translated as leptin. Leptin, resulted in the amount of fat and some central centers. The hypothesis that there may be a signal link in the site involved in regulating energy balance and reproduction has been used for more than 40 years to confirm that the leptin gene mutation and the leptin receptor gene mutation in .ob-ob and db/db(diabete gene, db- mice are similar to each other, respectively. Performance: severe early obesity, Severe insulin resistance, excessive diet, reduced energy consumption, infertility. However, after intraperitoneal injection of leptin to ob/ob mice, not only the body weight and food intake returned to normal level, but also the fertility was corrected. In female ob/ob rats, the weight of ovary and uterus increased, the concentration of luteinizing hormone (LH) increased, the number of primordial follicles and follicles increased, and the weight of testis and seminal vesicles increased in male ob/ob mice. These results suggest that leptin is involved in the regulation of reproductive function as well as food intake and energy expenditure. Although there is plenty of evidence to support the role of leptin in regulating reproductive function, whether leptin regulates the hypothalamus-pituitary-gonad axis directly or indirectly still requires more work to clarify. In this study, we studied the possible effect of leptin on hypothalamus in reproductive axis, and we hope that by observing the effect of leptin on the expression of neuropeptide Y in hypothalamic neuropeptide Y neurons, we can preliminarily explore the possible mechanism of leptin regulating reproduction. To provide some experimental basis for clinical application of leptin. The research contents and results are as follows:. Coexpression of Isob R and NPY in the hypothalamus of mice. Objective: leptin is a metabolic signal linking nutrition and reproduction, and plays an important role in the reproductive axis. Because the common expression of obR and obRmRNA and GnRH neurons in the central nervous system can not be found, most scholars believe that leptin acts indirectly on the secretion of GnRH neurons. NPY is one of the most important modulators involved in energy balance and neuroendocrine regulation. It is speculated that NPY may mediate the regulation between leptin and GnRH neurons. So we first observed the distribution of obR and NPY in the hypothalamus of mice. Then we observed the coexistence of the two in hypothalamus, and used them as the basis of the next experimental design. Methods: adult female C57bl-6J mice were treated with normal saline and 4% polymer via left ventricle.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2005
【分類(lèi)號(hào)】：R33

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