Orexin-A对肥胖模型大鼠杏仁核胃牵张敏感神经元放电活动及摄食的影响  

Effects of orexin-A on firing activity of gastric distension-sensitive neurons in the basomedial amygdala and food intake in diet-induced obese rats

作　　者：王咪 孙向荣[1] 郭菲菲[1] 栾晓[1] 徐珞[1] Wang Mi, Sun Xiangrong , Cuo Feifei, Luan Xiao , Xu Luo(Department of Pathophysiology, Qingdao University Medical College, Qingdao 266021, China)

机构地区：[1]青岛大学医学院病理生理学教研室,青岛266021

出　　处：《中华行为医学与脑科学杂志》2018年第9期769-776,共8页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金项目（81470815,81270460,81300281,81500414）;山东省优秀中青年科学家科研奖励基金项目（BS2014YY009）;中国博士后科学基金项目（2018M632627,2018M630749）

摘　　要：目的探讨食欲素A（orexin-A）对肥胖模型大鼠的基底内侧杏仁核（BMA）胃牵张敏感（GD）神经元放电活动及摄食量的影响及机制。方法选取健康雄性Wistar大鼠，高脂饮食诱导构建肥胖（DIO）和肥胖抵抗（DR）大鼠模型。采用细胞外记录神经元放电方法，观察orexin-A以及阿片受体拮抗剂纳洛酮对大鼠BMA GD神经元的影响；采用大鼠BMA置管药物微量注射术，观察orexin-A及纳洛酮对不同大鼠摄食的影响；应用RT-PCR和Elisa方法，检测大鼠BMA内orexin-1受体（OX-1R）及μ阿片受体的mRNA和蛋白含量的表达。结果BMA微量注射orexin-A后，正常大鼠GD敏感神经元放电频率显著增加[GD-E增幅：（78．3±6．9）％，GD-I增幅：（55．5±4．7）％，P〈0．01]，该效应可被OX-1R受体拮抗剂SB334867完全阻断，纳洛酮可部分阻断orexin-A的促放电效应。与正常大鼠相比，BMA注射orexin-A后DIO[GD-E增幅：（91．6±7．1）％，GD-I增幅：（67．9±8．1）％）]和DR[GD-E增幅：（87．9±6．8）％，GD-I增幅：（69．2±5．8）％]大鼠GD敏感神经元放电频率均显著增加（P〈0．05）。BMA注射orexin-A后可显著增加正常大鼠、DIO和DR大鼠的摄食量[分别是（2．38±0．34）g，（3．75±0．32）g，（4．01±0．38）g]，DR和DIO大鼠均显著高于正常大鼠（P〈0．05）。RT-PCR实验结果显示，DIO和DR大鼠OX-1R的mRNA（分别是5．85±0．45，6．03±0．42）高于正常大鼠，差异具有统计学意义（R〈0．05），DIO和DR大鼠μ阿片受体的mRNA（分别是（4．51±0．42），（8．31±0．41），高于正常大鼠（P〈0．05）。ELISA实验结果显示，DIO和DR大鼠OX-1R的蛋白含量[分别是（2．98±0．28）ng／μl，（3．05±0．31）ng／μl]高于正常大鼠[（1．53±0．31）ng／μl]（P〈0．05）；DR大鼠μ阿片受体蛋白含量[（4．21±0．35）ng／μl]高于DIO大鼠[（2．77±0．27）ng／μl]，且高于正常大�Objective To investigate the effects of orexin-A on firing activity of gastric distension- sensitive （GD） neurons in the basomedial amygdala （BMA） and food intake in diet-indaced obese rats. Methods Healthy male Wistar rats were selected,and the diet-induced obesity （DIO） rat model and diet- induced resistant （DR） rat model were established by high-fat diet. The effects of orexin-A and an opioid receptor antagonist naloxone on BMA GD neurons were observed by recording the extracellular potentials of single neurons. The effects of orexin-A and naloxone on the food intake of different rats were observed by using BMA catheterization. The mRNA expression and protein expression of orexin-1 receptor （OX-1R） and μ opiold receptor were detected by real-time PCR and Elisa,respectively. Results After microinjection of orexin- A into the BMA,the firing frequency of GD-sensitive neurons in the normal rats was significantly increased （ GD-E： （78.3± 6.9） %, GD-I： （ 55.5 ±4.7） %, P〈0.01 ）, and this effect was completely blocked by OX- 1R receptor antagonist SB334867, and naloxone partially blocked the discharge-promoting effect of orexin-A; Compared with the normal rats,the firing frequency of GD-sensitive neurons in the DIO（ GD-E： （91. 6± 7.1 ）% ,GD-I： （67.9±8.1）%） and DR（GD-E ： （87.9±6.8）% ,GD-I： （69.2±5.8） %） rats was significantly increased after BMA injection of orexin-A （P〈0. 05）. After administration of orexin-A into the BMA ,food intake of the normal rats,DIO rats and DR rats （ （2.38±0. 34） g,（3.75±0.32） g,（4.01±0.38） g,respectively） was significantly increased （P〈0. 01）, and the food intake of DR and DIO rats were significantly higher than that of normal rats （P〈0. 05 ）. After BMA was injected with naloxone, the food intake of rats was inhibited,and the food intake of the DIO rats was significantly lower than that of the DR rats （P〈0.05） ,food intake of the DR rats was significantly lower than that of

关 键 词：食欲素A 摄食 胃牵张敏感神经元 饮食诱导肥胖大鼠 杏仁核 

分 类 号：R589.2[医药卫生—内分泌] R-332[医药卫生—内科学]