α-MSH对大鼠下丘脑葡萄糖敏感神经元活动的调制作用

发布时间：2018-05-17 22:28

本文选题：α-黑色素细胞刺激素 + 下丘脑外侧区　；参考：《青岛大学》2011年硕士论文

【摘要】：由POMC神经元构成的中枢黑皮质素系统在机体的摄食及能量平衡的调控中发挥重要作用。a-MSH就是由POMC经过翻译后修饰裂解出具有生物学活性的黑皮质素家族成员之一。下丘脑与摄食调控密切相关的核团包括下丘脑外侧区(LHA)、下丘脑腹内侧核(VMH)、下丘脑室旁核(PVN)等,已知的黑皮质素的五种受体(MC1-5R)中只有MC3R和MC4R分布于下丘脑,a-MSH就是其内源性配体之一,通过参与Leptin的作用通路介导生理性的饱感信号。用α-MSH免疫后的大鼠摄食量比野生大鼠会有明显增加,且在第四脑室或迷走神经背核(DMV)注射MC3/4-R激动剂MTII会产生抑制摄食、体重下降的现象。我们已知在LHA中主要存在有葡萄糖抑制性神经元(GI),VMH中主要存在有葡萄糖兴奋型神经元(GE),而在PVN中则二者皆有。当外周静脉注射或者直接中枢核团内注射葡萄糖时,会使LHA的GI神经元放电频率减少而VMH的GE神经元放电频率增加,从而二者起到交互抑制的关系。所以我们推测通过作用于下丘脑不同核团的葡萄糖敏感神经元是a-MSH发挥其摄食调控效应的靶点之一。目的观察a-MSH (Alpha-Melanocyte stimulating hormone)对下丘脑外侧区(lateral hypothalamic area, LHA)、下丘脑腹内侧核(ventromedial hypothalamic nucleus, VMH)、下丘脑室旁核(paraventricular nucleus, PVN)部位葡萄糖兴奋型神经元和葡萄糖抑制型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。方法采用多管玻璃微电极记录单个细胞外单位放电的电生理学方法,以0.9% NaCl做为对照,在大鼠下丘脑不同核团微量注射a-MSH后观察葡萄糖敏感神经元的放电频率变化,再进一步观察微量注射拮抗剂SHU9119的基础上注射a-MSH对这两类神经元放电频率的影响。结果(1)在下丘脑外侧区(LHA)共记录到78个神经元,其中有46.15%(36/78)的神经元被鉴定为葡萄糖抑制型神经元(GI),36个GI神经元中有75%(27/36)被a-MSH抑制。对19个被a-MSH抑制的GI神经元,预先给予MC-4R的拮抗剂SHU9119,a-MSH的抑制效应部分被阻断。 (2)在下丘脑腹内侧核(VMH)共记录到56个神经元,39.28%(22/56)的神经元被鉴定为葡萄糖兴奋型神经元(GE),22个GE神经元中90.9%(20/22)被α-MSH兴奋。对10个被α-MSH兴奋的GE神经元预先给予SHU9119处理后,α-MSH的兴奋效应部分被阻断。 (3)在下丘脑室旁核(PVN)共记录到68个神经元,29.41%(20/68)被鉴定为GI神经元,39.71%(27/68)被鉴定为GE神经元。20个GI神经元中70%(14/20)被α-MSH抑制,27个GE神经元中88.88%(24/27)被α-MSH兴奋。对7个被α-MSH抑制的GI神经元和18个被α-MSH兴奋的GE神经元,均预先给予SHU9119,α-MSH效应亦部分被阻断。结论LHA内的大部分GI神经元被α-MSH所抑制,VMH内的大部分GE神经元被α-MSH所兴奋,α-MSH对PVN内的GI和GE神经元的兴奋性具有调制作用。这些结果表明下丘脑的葡萄敏感神经元可能是α-MSH参与中枢摄食调控的作用靶点之一。
[Abstract]:The central melanin system composed of POMC neurons plays an important role in the regulation of food intake and energy balance. A-MSH is one of the bioactive members of melanin family modified by POMC. The nuclei of hypothalamus closely related to feeding regulation include LHAA in lateral hypothalamus, VMHN in ventromedial hypothalamus, PVN in paraventricular nucleus of hypothalamus, etc. Of the five known receptors of melanin, MC1-5R, only MC3R and MC4R are endogenous ligands distributed in the hypothalamus, which mediate physiological satiety signals by participating in the pathway of Leptin. The food intake of rats immunized with 伪 -MSH was significantly higher than that of wild rats, and injection of MC3/4-R agonist MTII into the fourth ventricle or dorsal vagus nucleus of the rat could inhibit feeding and decrease body weight. It is known that there are mainly glucose-inhibitory neurons in LHA and both in PVN. When glucose was injected into the peripheral vein or directly into the central nucleus, the discharge frequency of GI neurons in LHA decreased and the discharge frequency of GE neurons in VMH increased. Therefore, we speculate that glucose-sensitive neurons acting on different nuclei of hypothalamus are one of the targets for a-MSH to exert its feeding regulation. Objective to investigate the modulating effects of a-MSH Alpha-Melanocyte stimulating on the discharges of glucose excitatory neurons and glucose inhibitory neurons in lateral hypothalamic area, LHAA, ventromedial hypothalamic nucleus, VMH, paraventricular nucleus of hypothalamus. To explore the possible mechanism of its participation in the regulation of food intake. Methods single extracellular unit discharges were recorded by multi-tube glass microelectrode. The frequency of glucose sensitive neurons was observed after microinjection of a-MSH into rat hypothalamus with 0.9% NaCl as control. The effects of microinjection of SHU9119 and a-MSH on the discharge frequency of these two kinds of neurons were further observed. Results (1) A total of 78 neurons were recorded in LHA of the lateral hypothalamus, of which 46.15 / 36 / 78) were identified as glucose-inhibited neurons and 7527 / 36 / 36 of 36 neurons were inhibited by a-MSH. The inhibitory effect of MC-4R antagonist SHU9119a-MSH on 19 GI neurons inhibited by a-MSH was partially blocked. (2) in the ventromedial hypothalamic nucleus (VMH), a total of 56 neurons (39.28 / 56) were identified as glucose excitatory neurons, and 90.9% 20% 22% of 22 GE neurons were excited by 伪 -MSH. After 10 GE neurons excited by 伪 -MSH were pretreated with SHU9119, the excitatory effect of 伪 -MSH was partially blocked. In PVN of hypothalamic paraventricular nucleus (PVN), a total of 68 neurons (29.41 / 68) were identified as GE neurons (39.71 / 68), 70 / 14 (20 / 20) of 20 GI neurons were inhibited by 伪 -MSH, and 88.8824 / 27 of 27 GE neurons were excited by 伪 -MSH. Seven GI neurons inhibited by 伪 -MSH and 18 GE neurons excited by 伪 -MSH were pretreated with SHU9119, and the 伪 -MSH effect was partially blocked. Conclusion most of the GI neurons in LHA are inhibited by 伪 -MSH. Most of GE neurons in LHA are excited by 伪 -MSH. 伪 -MSH modulates the excitability of GI and GE neurons in PVN. These results suggest that the grape sensitive neurons in the hypothalamus may be one of the targets of 伪 -MSH involved in the regulation of central feeding.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R338.2

【参考文献】