摘要
目的:研究转录因子FoxO 1抑制剂AS1842856在高脂饮食引起小鼠抑郁样行为中的作用。方法:本研究采用连续3周给予高脂饮食建立小鼠抑郁模型,通过灌胃给予FoxO 1选择性抑制剂AS1842856,采用蔗糖偏爱测试、社会交互行为测试、强迫游泳实验检测小鼠的抑郁样行为,最后采用酶联免疫吸附(ELISA)检测血清中炎症因子的水平。结果:高脂饮食可以诱导小鼠表现出抑郁样行为,高脂饮食小鼠的体重显著增加(P <0. 0001),蔗糖偏爱值显著降低(P <0. 0001),社会交互率降低(P <0. 0001),在强迫游泳实验中的不动时间显著增加(P <0. 0001)。此外,高脂饮食增加小鼠血清中炎症因子的水平,包括IL-6(P=0. 0001),IL-1β(P <0. 0001),TNFα(P=0. 0001)。口服给予小鼠FoxO 1抑制剂AS1842856可以逆转高脂饮食引起的抑郁样行为,即小鼠的蔗糖偏爱值增加(P=0. 0006),社会交互率增加(P <0. 0001),在强迫游泳实验中的不动时间减少(P=0. 0001)。结论:高脂饮食可以诱导小鼠表现出抑郁样行为,FoxO 1抑制剂AS1842856能够逆转高脂饮食引起的小鼠抑郁样行为。
Objective: To investigate the role of FoxO1 inhibitor AS1842856 in depression-like behaviors induced by high-fat diet in mice.Methods: In this study,3-week high-fat diet was used to establish a model of depression in mice. The FoxO1 inhibitor AS1842856 was orally administerated. The sucrose preference test,social interaction test and forced swimming test were used to detect the depression-like behaviors of mice. Additionally,enzyme-linked immunosorbent assay( ELISA) was used to measure the level of cytokine factors in serum.Results: Compared with normal chew,the weight of mice was significantly increased( P < 0. 0001),and the sucrose preference was significantly decreased( P <0. 0001),the interaction rate was reduced( P < 0. 0001) and the immobility time in forced swimming test was significantly increased( P < 0. 0001),the levels of cytokine factors in the serum of mice were increased,IL-6( P < 0. 0001),IL-1β( P < 0. 0001),TNFα( P < 0. 0001) in the high-fat diet group.Conclusion: The current findings suggest that FoxO1 inhibitors can reverse the depression-like behaviors in mice induced by high-fat diet.
作者
黄英杰
张为旭
丁增波
武潇
李素霞
朱维莉
HUANG Yingjie;ZHANG Weixu;DING Zengbo;WU Xiao;LI Suxia;ZHU Weili(Department of Pharmacology,School of Basic Medical Sciences,Peking University Health Science Center,Beijing,100191;National Institute on Drug Dependence,Peking University,Beijing,100191;School of Biological Science and Technology,Shenyang Agricultural University,Shenyang,110866)
出处
《中国药物依赖性杂志》
CAS
CSCD
2019年第6期426-431,455,共7页
Chinese Journal of Drug Dependence
基金
国家自然科学基金(81371489,81871071)资助。
