Nesfatin-1對大鼠腦干孤束核葡萄糖敏感神經(jīng)元電活動的影響
發(fā)布時間：2018-08-25 19:49
【摘要】： 背景資料：Nesfatin-1作為一種厭食肽,是由日本群馬大學(xué)森昌朋教授等發(fā)現(xiàn)的,主要分布在下丘腦室旁核(PVN)、視上核(SON)、腦干孤束核(NTS)、胃粘膜、胰腺等部位,饑餓時其表達(dá)將下調(diào)。腦室內(nèi)注射nesfatin-1可以抑制雄性Wistar大鼠和肥胖的Zucker大鼠的攝食達(dá)6個小時,呈劑量依賴性。外周注射nesfatin-1和它的中間片段可以抑制攝食達(dá)3小時。Nesfatin-1的中間片段可以減少瘦素抵抗肥胖大鼠的攝食量。外周注射nesfatin-1的中間片段可以引起孤束核的阿黑皮素原、可卡因和安非他命相關(guān)肽的mRNA的表達(dá),但是在下丘腦弓狀核沒有這種作用�，F(xiàn)在我們知道大鼠下丘腦含有調(diào)控攝食的特定分泌蛋白,其中nesfatin-1(其前體是NUCB2-一種功能尚未明確的分泌蛋白)可以調(diào)節(jié)大鼠攝食的下丘腦核團的表達(dá)。腦室內(nèi)注射NUCB2可以減少攝食量。大鼠腦脊液中含有nesfatin-1,它是NUCB2的氨基末端分離片段,在饑餓狀態(tài)下,其在下丘腦室旁核的表達(dá)下降。腦室內(nèi)注射nesfatin-1可以減少攝食,注射其抗體可以刺激攝食,呈劑量依賴性。然而,腦室內(nèi)注射NUCB2其他片段不會影響攝食,而且NUCB2必須轉(zhuǎn)化為nesfatin-1以后才能起到減少攝食的作用。Nesfatin-1誘導(dǎo)的饑餓可發(fā)生于瘦素基因突變的Zucker大鼠中,同時,抗nesfatin-1抗體不能阻斷瘦素誘導(dǎo)的饑餓。相反,中樞注射黑素細(xì)胞刺激激素可以上調(diào)室旁核NUCB2的基因表達(dá),而注射MC3/4受體拮抗劑以后使nesfatin-1誘導(dǎo)的飽感消失。這說明,nesfatin-1作為一種飽感分子可能和黑素細(xì)胞信號通路密切相關(guān)。 已知葡萄糖的水平對能量平衡的調(diào)控有很重要的作用,腦內(nèi)許多關(guān)鍵區(qū)域存在葡萄糖敏感神經(jīng)元,如下丘腦、NTS、杏仁核。當(dāng)細(xì)胞外葡萄糖濃度升高時,葡萄糖興奮型神經(jīng)元(glucose-EXC)的放電頻率增加,而葡萄糖抑制型神經(jīng)元(glucose-INH)的放電頻率降低。 目的：觀察nesfatin-1對大鼠腦干孤束核(Nucleus tractus solitarius,NTS)葡萄糖敏感神經(jīng)元的電活動影響,探討其抑制攝食作用的可能機制。 方法：采用全細(xì)胞膜片鉗技術(shù),在電流鉗下,記錄nesfatin-1對孤束核葡萄糖敏感神經(jīng)元電活動的影響。 結(jié)果：在孤束核記錄到43個神經(jīng)元,有31個對葡萄糖有反應(yīng),其中20個給予葡萄糖(5mmol/L)灌流后放電頻率升高伴膜電位絕對值減小(G-EXC),11個神經(jīng)元給予葡萄糖(5mmol/L)灌流后放電頻率下降并伴有膜電位絕對值增大(G-INH),其余12個給予葡萄糖(5mmol/L)灌流后無反應(yīng)。在20個G-EXC神經(jīng)元,其中18個灌流nesfatin-1 (10nmmol/L)使其放電頻率增加伴膜電位絕對值減小,2個無反應(yīng)。在11個G-INH神經(jīng)元,其中10個灌流nesfatin-1使其放電頻率減少并伴有膜電位絕對值增大1個無反應(yīng)。 結(jié)論：Nesfatin-1能夠調(diào)制孤束核葡萄糖敏感神經(jīng)元的興奮性,這可能是nesfatin-1作用于孤束核抑制攝食的機制之一。
[Abstract]:Background: Nesfatin-1, as an anorexic peptide, was discovered by Professor Sen Changpeng of Japanese Quomma University. It was mainly distributed in the paraventricular nucleus of the hypothalamus (PVN),) in the gastric mucosa and pancreas of (NTS), in the supraoptic nucleus of (SON), in the supraoptic nucleus of the paraventricular nucleus of the hypothalamus. The expression of Nesfatin-1 was down-regulated during starvation. Intraventricular injection of nesfatin-1 inhibited the feeding of male Wistar rats and obese Zucker rats for 6 hours in a dose-dependent manner. Peripheral injection of nesfatin-1 and its intermediate fragment could inhibit the intake of the intermediate fragment for 3 hours. Nesfatin-1 could reduce the intake of leptin against obesity in rats. Peripheral injection of the intermediate fragment of nesfatin-1 could induce the expression of mRNA in the nucleus tractus solitarii of the arcutin, cocaine and amphetamine-related peptides, but not in the arcuate nucleus of the hypothalamus. It is now known that the hypothalamus of the rat contains a specific secretory protein that regulates food intake, in which nesfatin-1 (the precursor of which is an undefined secretory protein of NUCB2-) regulates the expression of the nucleus hypothalamus in rats. Intraventricular injection of NUCB2 can reduce food intake. Nesfatin-1, was found in cerebrospinal fluid (CSF) of rats which was isolated from the amino end of NUCB2 and its expression in the paraventricular nucleus of hypothalamus decreased under starvation. Intraventricular injection of nesfatin-1 can reduce food intake, and its antibody can stimulate feeding in a dose-dependent manner. However, intracerebroventricular injection of other NUCB2 fragments did not affect food intake, and NUCB2 must be converted to nesfatin-1 to reduce feeding. Nesfatin-1 induced starvation may occur in Zucker rats with leptin gene mutations, and at the same time, Anti-nesfatin-1 antibodies do not block leptin-induced starvation. In contrast, central injection of melanocyte stimulating hormone upregulated the expression of NUCB2 gene in paraventricular nucleus, but the satiety induced by nesfatin-1 disappeared after injection of MC3/4 receptor antagonist. These results suggest that nnesfatin-1, as a saturation molecule, may be closely related to the melanocyte signaling pathway. Glucose levels are known to play an important role in the regulation of energy balance. Glucose sensitive neurons exist in many key areas of the brain, such as hypothalamus NTS and amygdala. When the concentration of extracellular glucose increased, the discharge frequency of glucose excitatory neurons (glucose-EXC) increased, while that of glucose-inhibited neurons (glucose-INH) decreased. Aim: to observe the effect of nesfatin-1 on the electrical activity of glucose-sensitive neurons in rat brain stem solitary tract nucleus (Nucleus tractus solitarius,NTS) and to explore the possible mechanism of inhibition of feeding. Methods: whole cell patch clamp technique was used to record the effect of nesfatin-1 on the electrical activity of glucose sensitive neurons in the nucleus tractus solitarii under the current clamp. Results: among 43 neurons recorded in the nucleus of the solitary tract, 31 neurons were responsive to glucose. Among them, 20 neurons were given glucose (5mmol/L) with increased discharge frequency and decreased absolute value of membrane potential (G-EXC), 11 neurons were treated with glucose (5mmol/L), the discharge frequency was decreased and the absolute value of membrane potential was increased (G-INH). The other 12 neurons had no response after 5mmol/L perfusion. In 20 G-EXC neurons, 18 of them were perfused with nesfatin-1 (10nmmol/L) to increase their discharge frequency and decrease the absolute value of membrane potential. In 11 G-INH neurons, 10 of them were perfused with nesfatin-1 to reduce their discharge frequency and to increase the absolute value of membrane potential by 1 non-response. ConclusionNesfatin-1 can modulate the excitability of glucose sensitive neurons in the nucleus of the solitary tract, which may be one of the mechanisms of the inhibitory effect of nesfatin-1 on the feeding of the nucleus of the solitary tract.
【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】：2010
【分類號】：R338.2
本文編號：2203923
[Abstract]:Background: Nesfatin-1, as an anorexic peptide, was discovered by Professor Sen Changpeng of Japanese Quomma University. It was mainly distributed in the paraventricular nucleus of the hypothalamus (PVN),) in the gastric mucosa and pancreas of (NTS), in the supraoptic nucleus of (SON), in the supraoptic nucleus of the paraventricular nucleus of the hypothalamus. The expression of Nesfatin-1 was down-regulated during starvation. Intraventricular injection of nesfatin-1 inhibited the feeding of male Wistar rats and obese Zucker rats for 6 hours in a dose-dependent manner. Peripheral injection of nesfatin-1 and its intermediate fragment could inhibit the intake of the intermediate fragment for 3 hours. Nesfatin-1 could reduce the intake of leptin against obesity in rats. Peripheral injection of the intermediate fragment of nesfatin-1 could induce the expression of mRNA in the nucleus tractus solitarii of the arcutin, cocaine and amphetamine-related peptides, but not in the arcuate nucleus of the hypothalamus. It is now known that the hypothalamus of the rat contains a specific secretory protein that regulates food intake, in which nesfatin-1 (the precursor of which is an undefined secretory protein of NUCB2-) regulates the expression of the nucleus hypothalamus in rats. Intraventricular injection of NUCB2 can reduce food intake. Nesfatin-1, was found in cerebrospinal fluid (CSF) of rats which was isolated from the amino end of NUCB2 and its expression in the paraventricular nucleus of hypothalamus decreased under starvation. Intraventricular injection of nesfatin-1 can reduce food intake, and its antibody can stimulate feeding in a dose-dependent manner. However, intracerebroventricular injection of other NUCB2 fragments did not affect food intake, and NUCB2 must be converted to nesfatin-1 to reduce feeding. Nesfatin-1 induced starvation may occur in Zucker rats with leptin gene mutations, and at the same time, Anti-nesfatin-1 antibodies do not block leptin-induced starvation. In contrast, central injection of melanocyte stimulating hormone upregulated the expression of NUCB2 gene in paraventricular nucleus, but the satiety induced by nesfatin-1 disappeared after injection of MC3/4 receptor antagonist. These results suggest that nnesfatin-1, as a saturation molecule, may be closely related to the melanocyte signaling pathway. Glucose levels are known to play an important role in the regulation of energy balance. Glucose sensitive neurons exist in many key areas of the brain, such as hypothalamus NTS and amygdala. When the concentration of extracellular glucose increased, the discharge frequency of glucose excitatory neurons (glucose-EXC) increased, while that of glucose-inhibited neurons (glucose-INH) decreased. Aim: to observe the effect of nesfatin-1 on the electrical activity of glucose-sensitive neurons in rat brain stem solitary tract nucleus (Nucleus tractus solitarius,NTS) and to explore the possible mechanism of inhibition of feeding. Methods: whole cell patch clamp technique was used to record the effect of nesfatin-1 on the electrical activity of glucose sensitive neurons in the nucleus tractus solitarii under the current clamp. Results: among 43 neurons recorded in the nucleus of the solitary tract, 31 neurons were responsive to glucose. Among them, 20 neurons were given glucose (5mmol/L) with increased discharge frequency and decreased absolute value of membrane potential (G-EXC), 11 neurons were treated with glucose (5mmol/L), the discharge frequency was decreased and the absolute value of membrane potential was increased (G-INH). The other 12 neurons had no response after 5mmol/L perfusion. In 20 G-EXC neurons, 18 of them were perfused with nesfatin-1 (10nmmol/L) to increase their discharge frequency and decrease the absolute value of membrane potential. In 11 G-INH neurons, 10 of them were perfused with nesfatin-1 to reduce their discharge frequency and to increase the absolute value of membrane potential by 1 non-response. ConclusionNesfatin-1 can modulate the excitability of glucose sensitive neurons in the nucleus of the solitary tract, which may be one of the mechanisms of the inhibitory effect of nesfatin-1 on the feeding of the nucleus of the solitary tract.
【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】：2010
【分類號】：R338.2
【共引文獻(xiàn)】
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2 冀躍科;Neuronostatin誘導(dǎo)小鼠抑郁樣作用的研究[D];蘭州大學(xué);2011年
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，本文編號：2203923
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