生长激素释放肽-6对小鼠下丘脑摄食相关核团c-fos表达时间依从性影响

发布时间：2018-09-19 13:19

【摘要】：本研究旨在探讨外周注射ghrelin受体激动剂生长激素释放肽-6(growth hormone releasing peptide-6,GHRP-6)对NMRI小鼠摄食的影响以及摄食相关核团(弓状核、视上核和室旁核)的激活情况及其有效作用时间。腹腔注射GHRP-6 1,3,6 h后观察小鼠累计摄食量,同时用免疫组织化学方法检测GHRP-6对自由饮食小鼠和禁食小鼠下丘脑摄食相关核团c-fos表达影响,并观察GHRP-6作用的时间依从性。结果显示,腹腔注射了GHRP-6的小鼠摄食量明显大于生理盐水注射鼠,且在注射后3 h时观察到的摄食量的增加尤为显著,但注射后6 h内总的累计摄食量无显著变化;同时,GHRP-6能够在不依赖于摄食的情况下促进弓状核和室旁核中c-fos的表达,且c-fos的表达在注射后1 h时达到峰值,随后逐渐下降。以上结果提示,外源性注入GHRP-6可显著增加动物在给药后1、3 h的累积摄食量,该作用至少部分是通过上调弓状核和室旁核中的c-fos蛋白表达起作用的,而且具有时间依从性。本研究结果可为临床ghrelin受体激动剂的使用间隔提供理论依据。
[Abstract]:The aim of this study was to investigate the effects of peripheral injection of growth hormone releasing peptide -6 (growth hormone releasing peptide-6,GHRP-6 (growth hormone releasing peptide-6,GHRP-6), a ghrelin receptor agonist, on the feeding of NMRI mice, as well as the activation of feeding related nuclei (arcuate nucleus, supraoptic nucleus and paraventricular nucleus) and their effective time. The cumulative food intake of mice was observed 6 hours after intraperitoneal injection of GHRP-6 1, and the effect of GHRP-6 on the expression of c-fos in hypothalamic feeding related nuclei of free diet mice and fasting mice was detected by immunohistochemical method, and the time compliance of GHRP-6 was observed. The results showed that the food intake of mice injected intraperitoneally with GHRP-6 was significantly higher than that of mice injected with normal saline, and the increase of food intake was especially significant at 3 h after injection, but there was no significant change in the total food intake within 6 h after injection. At the same time, GHRP-6 could promote the expression of c-fos in arcuate nucleus and paraventricular nucleus independently of feeding, and the expression of c-fos reached its peak at 1 h after injection, and then decreased gradually. These results suggest that exogenous injection of GHRP-6 can significantly increase the cumulative feeding intake of animals at 1h, at least partly by up-regulating the expression of c-fos protein in arcuate nucleus and paraventricular nucleus. The results of this study may provide a theoretical basis for the interval of use of ghrelin receptor agonists.
【作者单位】：青岛大学医学院;青岛大学医学院生理学教研室;鲁汶大学胃肠激素研究中心;
【基金】：supported by the National Natural Science Foundation of China(No.31371168)
【分类号】：R335

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