有氧运动改善肥胖易感大鼠食物奖赏:伏隔核CP-AMPARs介导的调控机制研究  

Aerobic Exercise Improves Food Reward in Obesity-prone Rats:Mediated by CP-AMPARs of Nucleus Accumbens

作　　者：魏龙威 牛亚凯 王振民 刘阳[1,2] 李娟 陈巍 WEI Longwei;NIU Yakai;WANG Zhenmin;LIU Yang;LI Juan;CHEN Wei(School of Physical Education,Hebei Normal University,Shijiazhuang 050024,China;Hebei Provincial Key Lab of Measurement and Evaluation in Human Movement and Bioinformation,Shijiazhuang 050024,China)

机构地区：[1]河北师范大学体育学院,河北石家庄050024 [2]河北省人体运动生物信息测评重点实验室,河北石家庄050024

出　　处：《体育科学》2022年第3期48-61,共14页China Sport Science

基　　金：国家自然科学基金项目(32071171);河北省高等学校科学技术研究项目(QN2020146)。

摘　　要：目的:揭示伏隔核Ca^(2+)渗透性AMPA受体(CP-AMPARs)在有氧运动改善肥胖易感大鼠食物奖赏中的作用机制。方法:60只雄性SD大鼠随机分为普通饮食组(C,n=15)和高脂饮食组(HFD,n=45),8周高脂饮食后从HFD大鼠中筛选肥胖抵抗组(OR,n=15)和肥胖易感组(OP,n=15),分别将其分为肥胖抵抗对照组(ORC,n=7)和肥胖抵抗运动组(ORE,n=7),肥胖易感对照组(OPC,n=7)和肥胖易感运动组(OPE,n=7)。ORE组与OPE组大鼠进行6周跑台运动干预(50 min/次、6次/周,起始速度14 m/min,每周递增2 m/min)。利用操作式条件反射进食行为实验与条件位置偏爱实验评价大鼠的进食动机及食物奖赏;通过观察注射CP-AMPARs选择性拮抗剂1-萘乙酰精胺(1-Naphthylacetyl spermine,NASPM)(20μg/0.5μL)后大鼠的进食行为变化,评价伏隔核CP-AMPARs在运动调节进食行为中的作用;使用在体多通道电生理技术检测伏隔核局部场电(local fieldpotentials,LFPs)及神经元活动;Westernblotting与免疫荧光双标技术检测伏隔核GluA1与GluA2蛋白表达。结果:与OR组大鼠比较,OP大鼠进食动机显著增高(P<0.01,P<0.05);与OPC大鼠比较,OPE大鼠进食动机显著降低(P<0.05);NASPM降低OPE大鼠进食动机较OPC大鼠更明显(P<0.05),伏隔核膜表面GluA1、GluA2阳性细胞及其共表达阳性细胞数量、GluA1与GluA2表达比值均显著降低(P<0.05);此外,与ORC大鼠比较,OPC大鼠伏隔核θ频段LFPs功率谱密度(P<0.01)、MSNs平均放电频率(P<0.01)及Spike-LFPs相干值(P<0.01)均显著升高;与OPC大鼠比较,OPE大鼠的上述变量均显著降低(P<0.01)。结论:6周有氧运动可改善肥胖易感大鼠食物奖赏,降低进食动机,并延缓体质量增长,其机制可能与有氧运动改变伏隔核膜表面GluA1∶GluA2表达,减少CP-AMPARs突触插入,降低伏隔核MSNs的Spike-LFPs异常同步活动有关。Objective:To explore the mechanism of nucleus accumbens calcium permeable AMPARs(CP-AMPARs)in improving food reward of obesity-prone rats by aerobic exercise.Methods:Sixty male SD rats were randomly divided into two groups:normal diet group(C,n=15)and high-fat diet group(HFD,n=45).After 8 weeks,the obesity-resistance group(OR,n=15)and obesity-prone group(OP,n=15)were selected from HFD.Then,OR and OP groups were divided into obesity-resistant control group(ORC,n=7)and obesity-resistant exercise group(ORE,n=7),obesity-prone control group(OPC,n=7)and obesity-prone exercise group(OPE,n=7),respectively.ORE rats and OPE rats were conducted a 6-week treadmill exercise intervention(50 min/time,6 times/week,starting speed 14 m/min,increasing 2 m/min per week),and instrumental conditioning test and conditioned place preference test were used to evaluate feeding motivation and food reward of rats.By observing the feeding behavior changes of rats after injection of 1-Naphthyl acetyl spermine(NASPM)(20μg/0.5μL),a selective antagonist of CP-AMPARs,the role of nucleus accumbens CP-AMPARs in motor regulation of eating behavior was evaluated.The local field potentials(LFPs)and neuronal activities in the nucleus accumbens were measured by in vivo multichannel electrophysiological technique.Western blotting and immunofluorescence double-labeling technique were used to detect the protein expression of GluA1 and GluA2 in the nucleus accumbens.Results:Compared with OR rats,the feeding motivation of OP rats was increased(P<0.01,P<0.05),but the feeding motivation of OPE rats was decreased(P<0.05).The NASPM injection decreased OPE rats feeding motivation more significantly than OPC rats(P<0.05),the number of GluA1,GluA2 positive cells and their co-expression positive cells and the ratio of GluA1 to GluA2 on the surface of the nucleus accumbens membrane were decreased(P<0.05).Furthermore,compared with ORC rats,the LFPs power spectral density in theta band of the nucleus accumbens of OPC rats(P<0.01),the mean discharge frequency of MSNs(

关 键 词：肥胖易感 食物奖赏 伏隔核 CP-AMPARs 有氧运动 

分 类 号：G804.2[文化科学—运动人体科学]