CaSR激动剂R568灌胃对小鼠摄食影响及机制  

EFFECT OF INTRAGASTRIC ADMINISTRATION OF CALCIUM-SENSITIVE RECEPTOR AGONIST R568 ON FOOD INTAKE OF MICE AND ITS MECHANISM

作　　者：韩冰[1] 郭亚杰 金婷婷 孙向荣[1] HAN Bing;GUO Yajie;JIN Tingting;SUN Xiangrong(Department of Physiology and Pathophysiology,School of Basic Medicine,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学基础医学院生理学与病理生理学系,山东青岛266071

出　　处：《青岛大学学报（医学版）》2023年第2期163-167,共5页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金面上项目(31971060)。

摘　　要：目的探讨钙离子敏感受体(CaSR)激动剂R568对小鼠食物摄入量的影响及其机制。方法将雄性KM小鼠随机分为R568组、二甲基亚砜(DMSO)组、胆囊收缩素A(CCKA)受体拮抗剂L-364,718+R568组和NPS-2143+R568组,每组8只,采用摄食分析方法,观察灌胃R568对小鼠食物摄入量的影响。将小鼠随机分为DMSO组和R568组(每组7只),采用酶联免疫吸附试验(ELISA)方法观察R568对小鼠血清、胃肠组织胃饥饿素(Ghrelin)、胆囊收缩素(CCK)、酪酪肽(PYY)、胰高血糖素样肽-1(GLP-1)及下丘脑CCK、Ghrelin含量变化的影响;采用荧光免疫组化染色方法,观察R568对下丘脑室旁核(PVN)、外侧区(LHA)、弓状核(ARC)中c-fos表达的影响。将小鼠分为DMSO组和R568组(n=7),采用高效液相色谱(HPLC)法观察R568对下丘脑神经递质多巴胺(DA)和5-羟色胺(5-HT)含量变化的影响。结果与DMSO组相比,R568灌胃后0~2 h内小鼠摄食量显著降低(F=5.274、5.225,P<0.01),并且这种作用能被CaSR阻断剂NPS-2143阻断;与DMSO组相比较,R568组胃和血清Ghrelin含量显著降低(t=2.995、4.939,P<0.05),近端小肠和血清CCK含量显著增高(t=3.223、4.970,P<0.05),而PYY和GLP-1无明显变化(P>0.05)。R568灌胃后小鼠下丘脑PVN、LHA、ARC中c-fos阳性细胞数目显著增加(t=3.508~6.169,P<0.01)。与DMSO组相比,R568灌胃后下丘脑DA含量显著减少(t=3.288,P<0.05),下丘脑5-HT、CCK及Ghrelin含量差异无显著性(P>0.05)。结论胃肠道CaSR激活后引起小鼠的摄食量减少,其作用机制与调节胃肠道CCK和Ghrelin分泌,调控下丘脑PVN、LHA、ARC神经元的兴奋性以及下丘脑DA的分泌有关。Objective To investigate the effect of the calcium-sensitive receptor(CaSR)agonist R568 on food intake of mice and its potential mechanism.Methods Male KM mice were randomly divided into R568 group,dimethyl sulfoxide(DMSO)group,cholecystokinin A(CCKA)receptor antagonist L-364,718+R568 group,and NPS-2143+R568 group,with 8 mice in each group,and the food intake analysis was performed to observe the effect of the intragastric administration of R568 on food intake of mice.Mice were randomly divided into DMSO group and R568 group,with 7 mice in each group;ELISA was used to observe the effect of R568 on the levels of Ghrelin,cholecystokinin(CCK),peptide YY(PYY),and glucagon-like peptide-1(GLP-1)in serum and gastrointestinal tissue and the content of CCK and ghrelin in the hypothalamus,and immunofluorescence was used to observe the effect of R568 on the expression of c-fos in the paraventricular nucleus(PVN),the lateral hypothalamic area(LHA),and the arcuate nucleus(ARC)of the hypothalamus.Mice were divided into DMSO group and R568 group,with 7 mice in each group,and high-performance liquid chromatography(HPLC)was used to observe the effect of R568 on the content of the neurotransmitters dopamine(DA)and serotonin(5-HT)in the hypothalamus.Results Compared with the DMSO group,the R568 group showed a significant reduction in food intake within 0-2 h after intragastric administration(F=5.274,5.225;P<0.05),and this effect was blocked by the CaSR antagonist NPS-2143;compared with the DMSO group,the R568 group had a significant reduction in the content of ghrelin in the stomach and serum(t=2.995,4.939;P<0.05)and a significant increase in the content of CCK in the proximal small intestine and serum(t=3.223,4.970;P<0.05),while there were no significant changes in PYY and GLP-1(P>0.05).In addition,there was a significant increase the number of c-fos-positive neurons in the PVN,LHA,and ARC after the intragastric administration of R568(t=3.508-6.169,P<0.05).Compared with the DMSO group,there was a significant reduction in the conte

关 键 词：受体 钙敏感 下丘脑 进食 神经肽类 多巴胺 

分 类 号：R363.2[医药卫生—病理学]