不同时间限制性饮食模式对小鼠生物节律和脑iNOS的调节作用  

Regulation of rhythm and brain iNOS levels in mice by different time-restricted feeding patterns

作　　者：冯梓琦 朱玲[2] 江舟[3] 万莉红[2,3] Feng Zi-qi;Zhu Ling;Jiang Zhou;Wan Li-hong(Top-notch Undergraduate Training Program 2.0,Grade 2019,West China School of Basic Medical Sciences&Forensic Medicine,Sichuan University,Chengdu 610041,China;Department of Pharmacology,West China School of Basic Medical Sciences&Forensic Medicine,Sichuan University,Chengdu 610041,China;NHC Key Laboratory of Chronobiology(Sichuan University),Sichuan University,Chengdu 610041,China)

机构地区：[1]明远学园——基础医学拔尖学生培养基地(怀德班),四川大学华西基础医学与法医学院,四川成都610041 [2]四川大学华西基础医学与法医学院药理学教研室,四川成都610041 [3]国家卫生健康委员会时间生物学重点实验室(四川大学),四川成都610041

出　　处：《四川生理科学杂志》2024年第7期1417-1420,共4页

基　　金：中央高校基本科研业务费专项资金资助(编号:SCU2023D022);西藏自治区科技计划项目(编号:CGZH2023000335);四川大学2022年基础学科拔尖人才培养研究课题重点项目(编号:SCUBJ110);。

摘　　要：目的:探究不同的时间限制性饮食(Time-restricted Feeding,TRF)模式对小鼠节律及脑内iNOS水平的影响差异。方法:选取SPF级雄性昆明小鼠36只,随机分为三组后放入节律箱驯化7 d,分别执行如下饮食模式24 d:a.节律晚期限制性饮食(顺节律时间TRF)(n=12):仅在ZT 15-ZT0开放饮食9 h;b.节律早期限制性饮食(逆节律时间TRF)组(n=12):仅在ZT 1.5-ZT10.5开放饮食9 h;c.自由饮食组(n=12):不限制饮食。在驯化第四天开始记录24 h自发活动并持续至执行TRF结束。次日于同时间点(ZT 0/6/12/18)各组分别取3只小鼠脑组织,采用Western Blot检测BMAL1和iNOS蛋白水平。结果:与自由饮食组相比,顺节律时间TRF不影响小鼠的正常活动节律,可减小BMAL1表达振幅,同时下调中枢iNOS水平(P<0.01);逆节律时间TRF组小鼠出现自发活动节律紊乱,BMAL1振幅高于顺节律组TRF小鼠,脑内iNOS水平显著高于顺节律时间TRF组小鼠(P<0.01)。结论:不同时间限制性饮食模式对小鼠节律和中枢iNOS水平的调节作用不同,顺节律时间TRF有助于维持健康的活动节律及中枢免疫稳态,而逆节律时间TRF会打破正常节律。Objective:To explore the differences in the effects of different time-restricted feeding patterns on mouse rhythms and brain iNOS levels.Methods:Thirty-six SPF male Kunming mice were randomly divided into 3 groups and placed in a rhythm box for 7 days of domestication.The following feeding patterns were performed for 24 days:a.Time-restricted feeding(TRF)in the late stage of rhythm(n=12):only open diet for 9 hours at ZT 15-ZT 0(synchronized with the rhythm);b.TRF in the early stage of rhythm(n=12):only open diet for 9 hours between ZT 1.5-ZT 10.5(not synchronized with the rhythm);c.Free diet(n=12):No dietary restrictions.On the fourth day of domestication,the spontaneous activities of 24 hours were recorded and lasted until the end of TRF.The next day at each of the following time points(ZT 0/6/12/18),three mouse brain tissues were taken from each group,and Western Blot was used to detect the levels of BMAL1 and iNOS proteins.Results:Compared with the free diet group,the rhythmic TRF did not affect the normal activity rhythm of mice but reduced the amplitude of BMAL1 expression and downregulated central iNOS levels(P<0.01).The reverse rhythmic TRF group mice exhibited spontaneous activity rhythm disorder,with higher amplitude of BMAL1 and significantly higher levels of iNOS in the brain compared to the rhythmic TRF group mice(P<0.01).Conclusion:Different time-restricted feeding patterns have different regulatory effects on mice's rhythm and central inflammation.The rhythmic TRF helps maintain a healthy activity rhythm and central iNOS levels,while the reverse rhythmic TRF breaks the normal rhythm.

关 键 词：时间限制性饮食 昼夜节律 生物钟 中枢免疫 BMAL1 

分 类 号：R285.5[医药卫生—中药学]