摘要
目的研究番茄红素(Lycopene,Lyc)对BTBR T^(+)Itpr3^(tf)/J(BTBR)自闭症模型小鼠海马组织中炎症水平、社交缺陷、认知障碍和重复刻板行为的影响。方法7~8周龄成年雄性健康C57BL/6(C57)与BTBR小鼠随机数字表法分为4组(n=8):C57+Veh组、C57+Lyc组、BTBR+Veh组、BTBR+Lyc组。C57+Lyc组和BTBR+Lyc组小鼠予以番茄红素(20 mg/kg)灌胃,1次/d,共7 d;C57+Veh组小鼠和BTBR+Veh组小鼠给予等体积的玉米油。给药7 d后开始三箱社交、雌雄交互、理毛、埋珠、开场实验、新物体识别、筑巢和Y迷宫等行为实验。结束后立即收取脑组织样本,进行RT-qPCR、Western blot实验。结果行为学结果显示:三箱社交实验中,BTBR+Veh组小鼠在陌生物体所在的箱体时间更多,表现出对陌生物体更偏好(P<0.05);而Lyc治疗后小鼠表现出对陌生小鼠更偏好(P<0.05)。理毛、埋珠实验中,BTBR+Veh组小鼠较C57+Veh组小鼠的重复刻板行为显著增多(P<0.05),Lyc治疗后显著减少了BTBR小鼠的重复刻板行为(P<0.05)。BTBR+Veh组小鼠较C57+Veh组小鼠海马组织中NLRP3炎症小体在mRNA和蛋白水平均显著增高(P<0.05);白细胞介素-1β(interleukin-1β,IL-1β)、IL-18、IL-6、核因子κB(nuclear factor kappaB,NF-κB)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)在mRNA水平显著增高(P<0.05);Lyc治疗后BTBR小鼠各炎症因子均显著降低(P<0.05)。结论番茄红素治疗通过降低BTBR小鼠海马中NLRP3炎症小体的水平,改善BTBR小鼠三箱社交缺陷和重复刻板行为。
Objective To investigate the effects of lycopene(Lyc)on hippocampal inflammation,social deficits and repetitive stereotyped behaviors in BTBR T^(+)Itpr3^(tf)/J autistic mice(BTBR,a mouse strain showing lower sociability as a model for autism spectrum disorder).Methods Adult male C57BL/6J(C57)and BTBR mice aged 7-8 weeks were randomly divided into(n=8):C57+Veh group,C57+Lyc group,BTBR+Veh group and BTBR+Lyc group.The mice from the C57+Lyc group and BTBR+Lyc group were given 20 mg/kg Lyc by gavage once a day for 7 d,and those of the C57+Veh group and BTBR+Veh mice were given equal volume of corn oil.Then three-chamber social test,male-female reciprocal social interactions,self-grooming,marble buying,open field test,object recognition test,nest building,and Y-maze test were conducted in these mice.Immediately after the behavioral tests,the mice were sacrificed and their brain samples were harvested for RT-qPCR and Western blotting.Results Behavioral results showed that in the three-chamber social test,the mice of the BTBR+Veh group spent longer time in the chamber with the object,showing much curiosity about the object(P<0.05),while the mice after Lyc treatment showed a preference for strange mice(P<0.05).In the self-grooming and marble burying behavior test,the BTBR+Veh group showed markedly increased repeated stereotyped behaviors than the C57+Veh group mice(P<0.05),which could be alleviated by Lyc treatment(P<0.05).The hippocampal expression of NLRP3 at mRNA and protein levels(P<0.05),and the mRNA levels of IL-1β,IL-18,IL-6,NF-κB,and TNF-αwere significantly increased in the BTBR+Veh group mice when compared with the C57+Veh group mice,and Lyc treatment obviously reversed above changes(P<0.05).Conclusion Lyc treatment improves three-chamber social deficits and repetitive stereotyped behaviors in BTBR mice by reducing NLRP3 inflammasome in the hippocampus of BTBR mice.
作者
李江辉
李达兵
朱先玉
陈梅
范晓棠
毛苹苏
LI Jianghui;LI Dabing;ZHU Xianyu;CHEN Mei;FAN Xiaotang;MAO Pingsu(Institute for Cancer Medicine,School of Basic Medical Sciences,Southwest Medical University,Luzhou,Sichuan Province,646000;Department of Military Cognitive Psychology,Faculty of Medical Psychology,Army Medical University(Third Military Medical University),Chongqing,400038,China;Department of Physiology,School of Basic Medical Sciences,Southwest Medical University,Luzhou,Sichuan Province,646000)
出处
《陆军军医大学学报》
CAS
CSCD
北大核心
2023年第14期1483-1492,共10页
Journal of Army Medical University
基金
国家自然科学基金面上项目(82071544)。
