本文選題：α-黑色素細(xì)胞刺激素 + 下丘腦外側(cè)區(qū)　； 參考：《青島大學(xué)》2011年碩士論文

【摘要】：由POMC神經(jīng)元構(gòu)成的中樞黑皮質(zhì)素系統(tǒng)在機體的攝食及能量平衡的調(diào)控中發(fā)揮重要作用。a-MSH就是由POMC經(jīng)過翻譯后修飾裂解出具有生物學(xué)活性的黑皮質(zhì)素家族成員之一。下丘腦與攝食調(diào)控密切相關(guān)的核團包括下丘腦外側(cè)區(qū)(LHA)、下丘腦腹內(nèi)側(cè)核(VMH)、下丘腦室旁核(PVN)等,已知的黑皮質(zhì)素的五種受體(MC1-5R)中只有MC3R和MC4R分布于下丘腦,a-MSH就是其內(nèi)源性配體之一,通過參與Leptin的作用通路介導(dǎo)生理性的飽感信號。用α-MSH免疫后的大鼠攝食量比野生大鼠會有明顯增加,且在第四腦室或迷走神經(jīng)背核(DMV)注射MC3/4-R激動劑MTII會產(chǎn)生抑制攝食、體重下降的現(xiàn)象。我們已知在LHA中主要存在有葡萄糖抑制性神經(jīng)元(GI),VMH中主要存在有葡萄糖興奮型神經(jīng)元(GE),而在PVN中則二者皆有。當(dāng)外周靜脈注射或者直接中樞核團內(nèi)注射葡萄糖時,會使LHA的GI神經(jīng)元放電頻率減少而VMH的GE神經(jīng)元放電頻率增加,從而二者起到交互抑制的關(guān)系。所以我們推測通過作用于下丘腦不同核團的葡萄糖敏感神經(jīng)元是a-MSH發(fā)揮其攝食調(diào)控效應(yīng)的靶點之一。 目的觀察a-MSH (Alpha-Melanocyte stimulating hormone)對下丘腦外側(cè)區(qū)(lateral hypothalamic area, LHA)、下丘腦腹內(nèi)側(cè)核(ventromedial hypothalamic nucleus, VMH)、下丘腦室旁核(paraventricular nucleus, PVN)部位葡萄糖興奮型神經(jīng)元和葡萄糖抑制型神經(jīng)元放電頻率的調(diào)制作用,探討其參與攝食調(diào)控的可能機制。 方法采用多管玻璃微電極記錄單個細(xì)胞外單位放電的電生理學(xué)方法,以0.9% NaCl做為對照,在大鼠下丘腦不同核團微量注射a-MSH后觀察葡萄糖敏感神經(jīng)元的放電頻率變化,再進一步觀察微量注射拮抗劑SHU9119的基礎(chǔ)上注射a-MSH對這兩類神經(jīng)元放電頻率的影響。 結(jié)果(1)在下丘腦外側(cè)區(qū)(LHA)共記錄到78個神經(jīng)元,其中有46.15%(36/78)的神經(jīng)元被鑒定為葡萄糖抑制型神經(jīng)元(GI),36個GI神經(jīng)元中有75%(27/36)被a-MSH抑制。對19個被a-MSH抑制的GI神經(jīng)元,預(yù)先給予MC-4R的拮抗劑SHU9119,a-MSH的抑制效應(yīng)部分被阻斷。 (2)在下丘腦腹內(nèi)側(cè)核(VMH)共記錄到56個神經(jīng)元,39.28%(22/56)的神經(jīng)元被鑒定為葡萄糖興奮型神經(jīng)元(GE),22個GE神經(jīng)元中90.9%(20/22)被α-MSH興奮。對10個被α-MSH興奮的GE神經(jīng)元預(yù)先給予SHU9119處理后,α-MSH的興奮效應(yīng)部分被阻斷。 (3)在下丘腦室旁核(PVN)共記錄到68個神經(jīng)元,29.41%(20/68)被鑒定為GI神經(jīng)元,39.71%(27/68)被鑒定為GE神經(jīng)元。20個GI神經(jīng)元中70%(14/20)被α-MSH抑制,27個GE神經(jīng)元中88.88%(24/27)被α-MSH興奮。對7個被α-MSH抑制的GI神經(jīng)元和18個被α-MSH興奮的GE神經(jīng)元,均預(yù)先給予SHU9119,α-MSH效應(yīng)亦部分被阻斷。 結(jié)論LHA內(nèi)的大部分GI神經(jīng)元被α-MSH所抑制,VMH內(nèi)的大部分GE神經(jīng)元被α-MSH所興奮,α-MSH對PVN內(nèi)的GI和GE神經(jīng)元的興奮性具有調(diào)制作用。這些結(jié)果表明下丘腦的葡萄敏感神經(jīng)元可能是α-MSH參與中樞攝食調(diào)控的作用靶點之一。
[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 偽 -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 偽 -MSH. After 10 GE neurons excited by 偽 -MSH were pretreated with SHU9119, the excitatory effect of 偽 -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 偽 -MSH, and 88.8824 / 27 of 27 GE neurons were excited by 偽 -MSH. Seven GI neurons inhibited by 偽 -MSH and 18 GE neurons excited by 偽 -MSH were pretreated with SHU9119, and the 偽 -MSH effect was partially blocked. Conclusion most of the GI neurons in LHA are inhibited by 偽 -MSH. Most of GE neurons in LHA are excited by 偽 -MSH. 偽 -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 偽 -MSH involved in the regulation of central feeding.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R338.2

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相關(guān)期刊論文 前1條

1 張曉紅;陳曦;蔣正堯;;α-MSH對大鼠背側(cè)迷走神經(jīng)復(fù)合體胃擴張敏感神經(jīng)元的作用[J];青島大學(xué)醫(yī)學(xué)院學(xué)報;2009年03期

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本文編號：1903155