调控采食量的神经肽——Orexin的研究进展

Orexin是1998年发现的一种肽类物质,其神经元主要分布在下丘脑。自orexin被发现的几年来,许多研究者对其进行了大量的研究。本文对orexin的结构、分布定位、生理功能做了相关综述,为orexin的应用研究做理论铺垫。     

鱼类下丘脑增食欲素(Orexin)研究进展

鱼体内的物质、能量代谢既与摄入食物、环境因素及运动强度有关,也与内分泌调控因子的参与密切相关。Orexin是新近发现的一种能够调节机体摄食和能量代谢的下丘脑神经多肽物质。目前在人类和其他哺乳动物上的研究越来越多,而在海洋鱼类上的研究则比较少见。本文首先综述了鱼类Orexin的基因、结构、组织分布与生理功能等方面的最新研究成果,初步阐明了Orexin在鱼类摄食、营养、生活节律等生理学基础领域中的作用,可为今后鱼类养殖领域开展该项目的应用性研究奠定基础。     

Hypothalamic expression of orexin A and lipid metabolism disorder in rats with alimentary obesity

AIM: To evaluate the effect of orexin A in rat hypothalamus on lipid metabolism disorder in rats with alimentary obesity induced by high-fat diet.METHODS: The rat model of alimentary obesity was induced by high-fat diet. The levels of insulin, triglyceride (TG) and total cholesterol (TC) in the serum were detected by luminescent immunoassay and enzymic method. The mRNA expression of orexin A in rat hypothalamus was determined by real-time PCR.RESULTS: There were statistically significant differences of weight, body fat content, and Lee's index between high-fat diet group and control group after 8-week feeding of high-fat diet. Compared to control animals, the levels of insulin, TG and TC in the rats with alimentary obesity significantly increased by 50％, 94％ and 43％, respectively (P<0.05). The expression of orexin A in rat hypothalamus significantly decreased by 57％, and had significant negative correlation with Lee's index, insulin, TG and TC. Their correlation coefficients were r=-0.798 (P<0.05), r=-0.868 (P<0.05), r=-0.981(P<0.05) and r=-0.815 (P<0.05), respectively. CONCLUSION: Alimentary obesity and lipid metabolism disorder induced by high-fat diet are correlated with down-regulation of orexin A expression in rat hypothalamus.     

兔脑和脊髓内开胃素A免疫阳性神经元和神经纤维的分布

采用免疫组织化学法研究了10只青紫蓝兔脑内开胃素（Orexin） A免疫阳性神经元和神经纤维的分布。结果显示，Orexin A免疫阳性神经元分布于下丘脑的视上核、室旁核、背内侧核、穹隆周核、外侧区、前区和后区以及底丘脑的未定带。Orexin A免疫阳性神经纤维广泛分布于中枢神经系统内，在端脑分布于大脑皮质、尾状核、隔核和杏仁核；在间脑分布于丘脑、下丘脑、上丘脑和垂体；在中脑分布于中央灰质、前丘、后丘、黑质、网状结构和中缝核；在脑桥分布于蓝斑、网状结构和中缝核；在延髓分布于极后区、孤束核和迷走神经背侧运动核；在小脑和脊髓也有分布。     

OX1R expression in chronic ischemic brain tissue of rats

AIM: To study the orexin-1 receptor (OX1R) expression in chronic ischemic brain tissue of rats and the change following the ischemic process.METHODS: The cerebral ischemic model was established by ligating double carotid arteries in rats. The behavior of the models was evaluated by water maze. The OX1R expression was determined by immunohistochemical technique, and the location of OX1R expression was further confirmed by double immunofluorescent staining.RESULTS: The intelligence of rats 15 d after ligating double carotid arteries was impaired obviously, and improved in 1 month and 2 months compared with the model in 15 d. At the same time, the OX1R expression increased obviously from acute phase until 15 d of cerebral ischemia and decreased notably in 1 month compared to the model in 15 d, and then increased significantly for the second time in 2 months of model. From the histology, partial neurons of 15 d model rats got atrophy, and most neurons in 1 month model rats got cytomorphosis and atrophy, however partial neurons in 2-month model rats recovered normally. The OX1R expression was confirmed in neurons definitely by double immunofluorescent staining.CONCLUSION: During the pathologic process of chronic ischemic injury, orexin system has two-way regulatory functions through.     

食欲素A对绵羊卵巢颗粒细胞P-AMPK与P-ERK信号通路的影响

为研究食欲素A对绵羊卵巢能量代谢及生长发育的调节作用,在体外培养黄体化颗粒细胞,用浓度为0.05,0.10μg/m L的食欲素A刺激细胞后,分别于0,2,6,12,24 h提取细胞总蛋白,采用Western Blot法对P-AMPK及P-ERK的表达量进行检测。结果显示,食欲素A刺激细胞2 h,0.05,0.10μg/m L剂量组的P-AMPK表达量与对照组相比均极显著提高(P0.01),食欲素A刺激细胞6 h,0.05,0.10μg/m L剂量组P-AMPK的表达量均达到最高值(P0.01),且0.10μg/m L剂量组表达量明显高于0.05μg/m L剂量组;食欲素A刺激细胞2 h,0.05,0.10μg/m L剂量组的P-ERK表达量与对照组相比均极显著提高(P0.01),食欲素A刺激细胞24 h,0.10μg/m L剂量组的P-ERK表达量极显著高于平台期(6~12 h)(P0.01)并达到最高值。表明食欲素A通过P-AMPK和P-ERK途径参与黄体能量代谢及生长发育的调节,从而进一步参与生殖机能的调控。     

食欲增食因子(Orexin)对动物采食的调节

本文主要介绍Orexin的基因及蛋白质结构、组织分布及其受体、Orexin与采食有关的各种生理功能及作用机制。     

Effects of orexigenic peptides and leptin on melatonin secretion during different photoperiods in seasonal breeding ewes: an in vitro study

The pineal gland (PG) acts as a neuroendocrine transducer of daily and seasonal time through the nocturnal release of melatonin. Here, we examined the interaction of season, orexin, ghrelin, and leptin on melatonin secretion by pineal explants in short-term culture. Glands were collected after sunset from 12 ewes during long days (LD; April and May) and from an additional 12 ewes during short days (SD; October and November). Glands were transected sagittally into strips, with each equilibrated in 2.5 mL of Dulbecco's modified Eagle's medium for 60 min, followed by a 2-h incubation in control medium or medium containing orexin B (10 and 100 ng/mL), ghrelin (10 and 100 ng/mL), or 50 ng/mL of leptin. After a 3-h incubation, some PG explants treated previously with lower doses of orexin or ghrelin were challenged with 50 ng/mL of leptin and those treated with both doses of orexin were challenged with 300 nM of the β-agonist isoproterenol. One milliliter of medium was harvested and replaced from each well every 30 min. Treatment with the low dose of orexin during LD increased melatonin secretion about 110% (P<0.01); treatment with a high dose increased melatonin secretion about 47% (P<0.001). During the SD period, leptin stimulated (P < 0.05) melatonin secretion slightly compared with mean melatonin concentration in controls. However, together, orexin and leptin depressed (P<0.01) melatonin secretion. Both doses of ghrelin reduced (P < 0.01) melatonin concentration during the SD season compared with control culture. Addition of ghrelin and leptin to culture medium increased (P<0.01) melatonin concentration compared with ghrelin-treated culture and decreased melatonin concentration (P<0.01) compared with leptin-treated culture during SD. Isoproterenol stimulated (P<0.01) melatonin secretion compared with values observed during the pretreatment period. We conclude that orexigenic peptides (orexin B and ghrelin) and an anorectic peptide (leptin) affect PG directly. The responses of PG to those hormones depend on day length. Moreover, secretion of melatonin from the ovine PG is under an adrenergic regulation.