Nesfatin-1对大鼠脑干孤束核葡萄糖敏感神经元电活动的影响
发布时间：2018-08-25 19:49
【摘要】： 背景资料：Nesfatin-1作为一种厌食肽,是由日本群马大学森昌朋教授等发现的,主要分布在下丘脑室旁核(PVN)、视上核(SON)、脑干孤束核(NTS)、胃粘膜、胰腺等部位,饥饿时其表达将下调。脑室内注射nesfatin-1可以抑制雄性Wistar大鼠和肥胖的Zucker大鼠的摄食达6个小时,呈剂量依赖性。外周注射nesfatin-1和它的中间片段可以抑制摄食达3小时。Nesfatin-1的中间片段可以减少瘦素抵抗肥胖大鼠的摄食量。外周注射nesfatin-1的中间片段可以引起孤束核的阿黑皮素原、可卡因和安非他命相关肽的mRNA的表达,但是在下丘脑弓状核没有这种作用。现在我们知道大鼠下丘脑含有调控摄食的特定分泌蛋白,其中nesfatin-1(其前体是NUCB2-一种功能尚未明确的分泌蛋白)可以调节大鼠摄食的下丘脑核团的表达。脑室内注射NUCB2可以减少摄食量。大鼠脑脊液中含有nesfatin-1,它是NUCB2的氨基末端分离片段,在饥饿状态下,其在下丘脑室旁核的表达下降。脑室内注射nesfatin-1可以减少摄食,注射其抗体可以刺激摄食,呈剂量依赖性。然而,脑室内注射NUCB2其他片段不会影响摄食,而且NUCB2必须转化为nesfatin-1以后才能起到减少摄食的作用。Nesfatin-1诱导的饥饿可发生于瘦素基因突变的Zucker大鼠中,同时,抗nesfatin-1抗体不能阻断瘦素诱导的饥饿。相反,中枢注射黑素细胞刺激激素可以上调室旁核NUCB2的基因表达,而注射MC3/4受体拮抗剂以后使nesfatin-1诱导的饱感消失。这说明,nesfatin-1作为一种饱感分子可能和黑素细胞信号通路密切相关。 已知葡萄糖的水平对能量平衡的调控有很重要的作用,脑内许多关键区域存在葡萄糖敏感神经元,如下丘脑、NTS、杏仁核。当细胞外葡萄糖浓度升高时,葡萄糖兴奋型神经元(glucose-EXC)的放电频率增加,而葡萄糖抑制型神经元(glucose-INH)的放电频率降低。 目的：观察nesfatin-1对大鼠脑干孤束核(Nucleus tractus solitarius,NTS)葡萄糖敏感神经元的电活动影响,探讨其抑制摄食作用的可能机制。 方法：采用全细胞膜片钳技术,在电流钳下,记录nesfatin-1对孤束核葡萄糖敏感神经元电活动的影响。 结果：在孤束核记录到43个神经元,有31个对葡萄糖有反应,其中20个给予葡萄糖(5mmol/L)灌流后放电频率升高伴膜电位绝对值减小(G-EXC),11个神经元给予葡萄糖(5mmol/L)灌流后放电频率下降并伴有膜电位绝对值增大(G-INH),其余12个给予葡萄糖(5mmol/L)灌流后无反应。在20个G-EXC神经元,其中18个灌流nesfatin-1 (10nmmol/L)使其放电频率增加伴膜电位绝对值减小,2个无反应。在11个G-INH神经元,其中10个灌流nesfatin-1使其放电频率减少并伴有膜电位绝对值增大1个无反应。 结论：Nesfatin-1能够调制孤束核葡萄糖敏感神经元的兴奋性,这可能是nesfatin-1作用于孤束核抑制摄食的机制之一。
[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.
【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
本文编号：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.
【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
【共引文献】
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