有氧运动干预CUMS小鼠海马神经炎症及改善NF-κB、TNF-α/IDO/5-HT信号通路的调控机制研究  

Effect of aerobic exercise on hippocampal neuroinflammation and improvement of NF-κB,TNF-α/IDO/5-HT signal pathway against in CUMS depressive mice

作　　者：刘瑞莲[1] 屈红林[1] LIU Rui-Lian;QU Hong-Lin(College of Physical Education,Yichun University,Yichun 336000,China)

机构地区：[1]宜春学院体育科学研究所,宜春336000

出　　处：《中国免疫学杂志》2021年第13期1563-1570,共8页Chinese Journal of Immunology

基　　金：江西省自然科学基金重点项目(20202ACBL206006);江西省教育厅科技项目(GJJ190849)。

摘　　要：目的:研究有氧运动的抗慢性应激性抑郁海马炎症及对色氨酸、犬尿氨酸(KYN)通路关键代谢酶吲哚胺2,3过氧化酶(IDO)及炎症相关NF-κB、TNF-α/IDO/5-HT信号通路的影响。方法:针对13种慢性应激刺激,采用随机数字法,每日1~2种刺激因素进行28 d的小鼠抑郁造模,Noldus EthoVision XT9系统采集分析小鼠强迫游泳(FST)、强迫悬尾(TST)不动时间,IDO、NF-κB、TNF-α、5-HT和多巴胺(DA)试剂盒检测实验小鼠海马组织中相关因子含量,Nissl染色观察小鼠海马Nissl体形态及数量,HE染色观察海马神经细胞的病理学改变,RT-qPCR验证海马组织中IDO、NF-κB、TNF-α、5-HT的mRNA表达,Western blot判定蛋白表达水平。结果:慢性应激性刺激4周后,模型组小鼠FST和TST不动时间明显延长(P<0.05),尼氏体核固缩并伴有空泡样病变,神经元细胞减少且排列紊乱,海马组织单胺类神经递质5-HT与DA含量减少,色氨酸代谢产物KYN含量增加,IDO、NF-κB、TNF-α生物活性增高,IDO、NF-κB、TNF-αmRNA表达上调,而5-HT mRNA表达下调(P<0.01)。有氧运动能缩短小鼠不动时间,改善尼氏体核固缩与空泡样病变,增加海马神经元数量,增加5-HT与DA含量的同时,降低KYN含量,抑制IDO、NF-κB、TNF-α活性,下调IDO、NF-κB、TNF-αmRNA表达,上调5-HT mRNA表达。结论:有氧运动对慢性应激性抑郁症小鼠具有抗抑郁效果,这一作用与抑制炎症因子诱导的IDO激活有关,其作用可能通过抑制NF-κB、TNF-α等炎症因子的表达,降低IDO活性,减少色氨酸等的代谢通路产物KYN的含量,增加5-HT合成,促进和改善海马认知功能障碍,发挥潜在的抗炎、抗抑郁作用,且这一作用机制可能与NF-κB、TNF-α/IDO/5-HT信号通路的作用有关。Objective:To study the effect of aerobic exercise on anti-chronic stress depression and key metabolic enzymes indoleamine 2,3 peroxidase(IDO)of tryptophan and kynurenine(KYN)pathway which was related to inflammatory of NF-κB,TNF-α/IDO/5-HT Pathway.Methods:Adopt the method of random numbers to make depression modelling for mice with 1 or 2 kinds of stimulating factors for 28 d in view of the 13 kinds of chronic stress stimulation.Collect and analyse motionless time for forced swim test(FST)and tail suspension test(TST)of mice by using Noldus EthoVision XT9 system.Relevant factors in hippocampus of experimental mice with IDO,NF-κB,TNF-α,5-HT,KYN and dopamine(DA)were detected by kits,and observed the morphology and number of Nissl by Nissl staining,and detected the pathological changes of hippocampal neurons by HE staining.Make RT-qPCR verification of mRNA expression of IDO,NF-κB,TNF-αand 5-HT in hippocampus.Western blot was used to detect protein of IDO,NF-κB and TNF-α.Results:After 4 weeks of chronic stress stimulation,the motionless time for FST and TST of mice in the model group obviously prolonged.And then,the nissl nucleus pyknosis with vacuolar-like pathological changes,neuronal cells decreased and disordered,hippocampus monoamine neurotransmitters 5-HT and DA content decreased,tryptophan metabolite KYN content increased.Bioactivity of IDO,NF-κB and TNF-αin hippocampus increased.mRNA expression of IDO,NF-κB and TNF-αin hippocampus increased,while mRNA expression of 5-HT decreased.Aerobic exercise could shorten the motionless time of mice,improve Nissl′s nucleus pyknosis and vacuole-like lesions,increase number of hippocampal neurons and content of 5-HT and DA,and decrease the KYN content,inhibit activity of IDO,NF-κB and TNF-α,reduce mRNA expression quantity of IDO,NF-κB and TNF-αand enhance expression of5-HT.Conclusion:Aerobic exercise has an antidepressant effect on mice for chronic stress depression,which is related to IDO activation induced by inhibit inflammatory cytokines.Effect might

关 键 词：有氧运动 抑郁症 慢性应激 吲哚胺2 3过氧化酶 

分 类 号：R875[医药卫生—运动医学]