摘要
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.
作者
文松
阮氏琼娥
萧文泽
王朝迅
龚敏
金建兰
周里钢
WEN Song;Thiquynhnga NGUYEN;XIAO Wen-Ze;WANG Chao-Xun;GONG Min;JIN Jian-Lan;ZHOU Li-Gang(Department of Endocrinology,Shanghai Pudong Hospital,Fudan University,Shanghai 201399,China)
出处
《生理学报》
CAS
CSCD
北大核心
2019年第4期514-526,共13页
Acta Physiologica Sinica
基金
supported by the National Natural Science Foundation of China(No.81370932)
the United States MERCK IISP Fund(No.40313,40309)
Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai Municipality,China(No.PWR12014-06)
Integrative Medicine Special Fund of Shanghai Municipal Health Planning Committee(No.ZHYY-ZXYJHZX-2-201712)
Key Studies(Special)Department Fund of the Pudong New Area Health Planning Commission,China(No.PWZzk2017-03)