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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 purpose of this study was to investigate the effects of ghrelin receptor agonist GHRP-6 on food intake in NMRI mice and the ingestion of related nuclei (arcuate nucleus, supraoptic nucleus And paraventricular nucleus) activation and its effective role in time. The 1,3,6 and 6 h after intraperitoneal injection of GHRP-6, the cumulative food intake was observed, and immunohistochemistry was used to detect GHRP-6 on free diet mice and fasted mice hypothalamic feeding related c-fos expression , And observed the time-dependent effects of GHRP-6. The results showed that GHRP-6 injected intraperitoneally in mice was significantly larger than saline-injected mice, and the increase in the amount of food intake observed at 3 h after injection was particularly significant, but the total cumulative intake within 6 h after injection , While GHRP-6 promoted the expression of c-fos in arcuate nucleus and paraventricular nucleus independent of food intake. The expression of c-fos peaked at 1 h after injection and then decreased gradually. The above results suggest that the exogenous injection of GHRP-6 significantly increased the cumulative food intake of animals at 1 and 3 h after administration, at least in part, by up-regulating c-fos protein expression in the arcuate nucleus and paraventricular nucleus And there is time compliance. The results of this study provide a theoretical basis for the clinical use of ghrelin receptor agonists.