leptin调节下丘脑神经肽Y分泌的研究

发布时间：2018-03-12 17:22

本文选题：leptin　切入点：神经肽Y　出处：《河北医科大学》2005年博士论文　论文类型：学位论文

【摘要】：1994 年,Zhang 等学者利用定位克隆技术成功克隆了小鼠的肥胖基因(obese gene, ob )及人类的同源序列,ob 基因编码的蛋白质产物被称为leptin,译为瘦素。leptin 的发现使脂肪量和某些中枢部位可能存在着一定信号联系参与调节能量平衡和生殖这一存在了40 多年的假说得以证实。ob/ob 鼠和db/db(diabete gene, db)鼠分别由于leptin 基因突变和leptin 受体的基因突变而具有相似的表现:严重的早发肥胖,严重的胰岛素抵抗,饮食过多,能耗降低,不孕不育。但是,给予ob/ob 鼠腹腔注射leptin 后,不仅体重和摄食恢复至正常水平,生育能力也得以纠正;在雌性ob/ob 鼠卵巢和子宫的重量增加,血清黄体生成素(luteinizing hormone,LH)浓度增加,原始卵泡和囊状卵泡数量增多;在雄性ob/ob 鼠睾丸和精囊腺重量增加,生成精子数量增多。这些实验结果说明leptin 在调节摄食与能量消耗的同时也参与了对生殖功能的调控。尽管有大量的证据支持leptin 调节生殖功能的角色,然而leptin 究竟是直接还是间接调节下丘脑-垂体-性腺轴,仍旧需要更多的工作去阐明。因此,本实验研究leptin 对生殖轴中下丘脑的可能作用,期望通过观察leptin 对下丘脑神经肽Y 神经元(Neuropeptide Y, NPY)表达的影响,能够初步探讨leptin 调控生殖的可能作用机理,为leptin 的临床应用提供一定的实验依据。研究内容与结果如下: 一、obR 与NPY 在小鼠下丘脑的共表达目的:leptin 是连接营养与生殖的代谢信号,在生殖轴中发挥重要作用。由于未能发现obR 和obRmRNA 与GnRH 神经元在中枢的共性表达,大多数学者认为leptin 是间接作用于GnRH 神经元影响其分泌,而NPY 是目前研究最多的参与能量平衡和神经内分泌调控的重要调质,推测NPY可能介导了leptin 和GnRH 神经元之间的调节作用。所以实验中我们首先观察obR 与NPY 在小鼠下丘脑的分布,然后进一步观察两者在下丘脑的是否有共存情况,并以此作为下一步实验设计的依据。方法:选用成年雌性C57bl/6J 小鼠,经左心室用生理盐水和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.
【学位授予单位】：河北医科大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R33

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