迷走复合体微量注射Nesfatin-1对摄食及葡萄糖敏感神经元的作用

发布时间：2018-02-24 04:08

本文关键词： 电生理 nesfatin-1 迷走神经复合体(DVC) 葡萄糖敏感神经元摄食　出处：《青岛大学》2010年硕士论文　论文类型：学位论文

【摘要】： Nesfatin-1是一个由82个氨基酸组成的多肽,侧脑室注射后可以抑制摄食,nesfatin-1是其中一个分泌片段,其前体蛋白nucleobindin2(NUCB2)经过激素转化酶的裂解作用生成三个片段,一个N端片段(nesfatin-1)和两个C端片段(nesfatin-2和nesfatin-3)。1侧脑室注射nesfatin-1有抑制摄食的作用并且呈现剂量依赖效应,注射其抗体后摄食增加。然而侧脑室注射nesfatin-2和nesfatin-3并不能增强饱感,因而NUCB2只有转化为nesfatin-1才能起到抑制摄食的作用。长期侧脑室注射nesfatin-1可以使体重减轻,而长期注射其抗体则使体重增加。在leptin受体突变的大鼠nesfatin-1可以使摄食减少,注射nesfatin-1的抗体并不能阻断leptin导致的摄食减少。这可以说明NUCB2是非依赖leptin的饱食分子。另外中枢注射α-MSH可以使NUCB2基因在室旁核表达增加,并且由nesfatin-1引起的饱食作用可以被α-MSH受体的拮抗剂所拮抗。所以我们认为nesfatin-1抑制摄食的作用机制与下丘脑的促黑激素信号系统有关。目的观察nesfatin-1对大鼠迷走神经复合体(dorsal vagal complex, DVC)胃扩张敏感神经元和葡萄糖感受神经元放电频率的调制作用,探讨其参与摄食调控的可能机制。观察DVC注射nesfatin-1对摄食的影响方法1)采用多管玻璃微电极记录单个细胞单位放电的电生理学方法,观察大鼠DVC区微量注射nesfatin-1前后上述两种神经元放电频率的变化,以微量注射0.9% NaCl作对照。2)采用行为学方法观察DVC区微量注射nesfatin-1前后摄食量和体重的变化。以微量注射0.9% NaCl作对照。结果1)在DVC中记录到的109个神经元经多管微电极给予葡萄糖,有46个放电频率降低(鉴定为G-INH);31个放电频率升高(鉴定为G-EXC);32个对葡萄糖没有反应。在39个G-INH经多管微电极给予nesfatin-1,有33个神经元放电频率降低,1个放电频率升高,5个对nesfatin-1无反应。在26个G-EXC神经元中,有20个放电频率升高,3个神经元放电频率降低,3个对nesfatin-1无反应。 2)在DVC中记录到89个神经元对其进行胃扩张(GD)刺激,48个神经元被激活(鉴定为GD-EXC),21个神经元被抑制(鉴定为GD-INH),其余20个神经元对胃扩张无反应。在42个GD-EXC神经元,其中32个被nesfatin-1所兴奋,10个对nesfatin-1无反应。在18个GD-INH神经元,16个被nesfatin-1所抑制,2个无反应。上述两类神经元经多管微电极给予0.9%NaCl,注射前后神经元放电频率的变化无统计学意义。 3)DVC内微量注射nesfatin-1后摄食量减少,体重减轻。结论Nesfatin-1能够调制DVC胃扩张敏感神经元和葡萄糖感受神经元的兴奋性,可以使大鼠摄食减少,体重减轻。这可能是nesfatin-1抑制摄食的部分机制。
[Abstract]:Nesfatin-1 is a peptide composed of 82 amino acids, which can be inhibited by intracerebroventricular injection. The precursor protein nucleobindin2nu CB2 (nucleobindin2nu CB2) is one of the secretory fragments, which can be divided into three fragments by glucocorticoid converting enzyme cleavage. One N-terminal fragment, one N-terminal fragment, and two C-terminal fragments, nesfatin-1, and two C-terminal fragments, nesfatin-1 injection into the lateral ventricle of nesfatin-3).1, had a dose-dependent effect on the inhibition of food intake. However, the injection of nesfatin-2 and nesfatin-3 into the lateral ventricle could not enhance the satiety. Long term intraventricular injection of nesfatin-1 can reduce body weight, while long term injection of its antibody can result in weight gain. In rats with leptin receptor mutation, nesfatin-1 can reduce food intake. The antibody injected with nesfatin-1 could not block the decrease of food intake induced by leptin, which indicated that NUCB2 was not dependent on leptin. In addition, 伪 -MSH could increase the expression of NUCB2 gene in paraventricular nucleus after central injection of 伪 -MSH. The satiety induced by nesfatin-1 can be antagonized by 伪 -MSH receptor antagonist. Therefore, we think that the mechanism of nesfatin-1 inhibiting feeding is related to the signal system of melanotropic hormone in hypothalamus. Objective to observe the modulating effect of nesfatin-1 on the frequency of gastric dilatation sensitive neurons and glucose-sensing neurons in rat vagal complex vagal complex (DVCs), and to explore the possible mechanism of its involvement in the regulation of feeding. To observe the effect of DVC injection of nesfatin-1 on feeding. Methods 1) the electrophysiological method of recording single cell unit discharge with multi-tube glass microelectrode was used to observe the changes of discharge frequency of the two neurons before and after microinjection of nesfatin-1 into the DVC region of rats. The changes of food intake and body weight before and after microinjection of nesfatin-1 in DVC area were observed by using microinjection of 0.9% NaCl as control group, and 0.9% NaCl as control. Results 1) 109 neurons recorded in DVC were given glucose via multi-tube microelectrode. Forty-six discharges decreased (identified as G-INHN; 31 increased (identified as G-EXCN; 32 were not responsive to glucose). In 39 G-INH treated with multitube microelectrode, the discharge frequency of 33 neurons decreased and 1 increased. In 26 G-EXC neurons, The discharges were increased in 20 neurons, decreased in 3 neurons, and showed no response to nesfatin-1 in 3 neurons. 2) 89 neurons were recorded in DVC stimulated by gastric dilatation, 48 neurons were activated (identified as GD-EXCN, 21 neurons were inhibited (identified as GD-INHN), the remaining 20 neurons were not responsive to gastric dilatation. 32 of them were excited by nesfatin-1, 10 did not respond to nesfatin-1, 18 GD-INH neurons were inhibited by nesfatin-1, 16 neurons were inhibited by nesfatin-1, and 2 neurons were not reacted. The two types of neurons were given 0.9g Na Cll with multiple microelectrodes. There was no significant difference in the frequency of neuronal discharge before and after injection. After microinjection of nesfatin-1, the food intake decreased and the body weight decreased. Conclusion Nesfatin-1 can modulate the excitability of DVC gastric dilatation sensitive neurons and glucose-sensing neurons, which may be the mechanism of nesfatin-1 inhibiting feeding.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R338.2

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