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  

Time course study of growth hormone releasing peptide-6-induced c-fos expression in neurons of feeding-related nuclei of hypothalamus

作　　者：俞燕娟 董静[1,2] 蒋正尧[2] Inge Depoortere 

机构地区：[1]青岛大学医学院,青岛266071 [2]青岛大学医学院生理学教研室,青岛266071 [3]鲁汶大学胃肠激素研究中心,比利时鲁汶

出　　处：《生理学报》2016年第1期19-26,共8页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China(No.31371168)

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。The present study was aimed to explore the effects of intraperitoneal injection of growth hormone releasing peptide-6（GHRP-6）,a ghrelin receptor agonist,on food intake and neuronal activity of feeding-related nuclei in the hypothalamus of NMRI mice. Accumulated amount of food intake was measured,and total number of c-fos immunoreactive neurons in arcuate nucleus（ARC）,paraventricular nucleus（PVN） and supraoptic nucleus（SON） was counted by immunohistochemistry at 1,3 and 6 h after the GHRP-6 injection. The results showed that GHRP-6 significantly increased the amount of food intake with a peak at 3 h after the GHRP-6 injection. Meanwhile,GHRP-6 could promote c-fos expression in the ARC and PVN independent of food intake,and the total number of c-fos immunoreactive neurons was peaked at 1 h after injection and then decreased gradually. These results suggest that GHRP-6 may increase food intake in time-dependent manner,which is associated with up-regulations of c-fos protein expression in the ARC and PVN.

关 键 词：生长激素释放肽-6 摄食 下丘脑 C-FOS 

分 类 号：R335[医药卫生—人体生理学]