胰高血糖素样肽-1受体激动剂抑制大鼠进食效应的比较研究（英文）

Comparative study on anorexigenic effect of glucagon-like peptide-1 receptor agonists in rats

胰高血糖素样肽-1 (glucagon-like peptide-1, GLP-1)在小肠细胞和脑干神经元中都有表达,起着抑制进食的作用。然而,目前对生理状态下影响进食的GLP-1的来源或是GLP-1受体激动剂(GLP-1 receptor agonists, GLP-1RA)的相关作用机制尚不明确。本研究选择即刻早期基因产物c-Fos作为特异抗原进行免疫组化染色以显示被GLP-1RA激活的中枢神经系统特定区域。将30只正常SD大鼠随机分为3组,分别一次性腹腔注射利拉鲁肽(200μg/kg)、艾塞那肽(10μg/kg)和生理盐水,检测给药后早期大鼠的摄食总量和血糖。结果显示,急性腹腔注射药理浓度的GLP-1RA能显著地影响摄食。然而,血糖的比较研究显示,在正常大鼠,GLP-1RA抑制进食的作用可能与血糖的变化相分离。与对照组相比,GLP-1RA组c-Fos表达主要在与摄食相关的核团中显著升高,并且在脊髓中发现了c-Fos的表达。以上结果果提示,急性注射药理浓度的GLP-1可以通过循环和迷走神经的途径影响中枢神经系统,尤其是作用于弓状核(arcuate nucleus, ARC)和孤束核(nucleus of solitary tract, NTS),GLP-1能同时调节自主神经的活动。

Glucagon-like peptide-1(GLP-1)expression is shared by both intestinal cells and neurons of brainstem,which plays anorexigenic role on food intake.However,the exact source of physiological GLP-1 influencing food intake and pertinent mechanism of GLP-1 receptor agonists(GLP-1 RA)remain unelucidated.In this study,the immediate early gene product c-Fos was chosen as the specific antigen for immunohistochemistry to show the certain areas of central nervous system(CNS)activation by the GLP-1 RA.Thirty normal SD rats were randomly assigned to 3 groups,which were single intraperitoneally injected with Liraglutide(200μg/kg),Exenatide(10μg/kg)and saline,respectively.After injection,the amount of food intake and acute glycemic variation were assessed for comparison.The results showed that acute pharmacological dosage of GLP-1 RA(Liraglutide or Exenatide)could significantly influence food intake.However,glycemic change indicated that the anorexic effect was dissociated with change in blood glucose in normal rats.Moreover,c-Fos was expressed significantly higher in major critical nuclei related to food intake in GLP-1 RA groups when compared with the control group,and its expression was also found in spinal cord.The results suggested that acute administration of pharmacological doses of GLP-1 influences CNS via circulation and vagal pathways,especially on the arcuate nucleus(ARC)and the nucleus of solitary tract(NTS),and GLP-1 modulates autonomic nervous activities.