摘要
目的基于Toll样受体4(TLR4)/核因子κB(NF-κB)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症体信号通路探究氟西汀对慢性不可预知性轻度应激(CUMS)模型大鼠抑郁样行为的作用。方法18只SD大鼠随机分为对照组、模型组和氟西汀组。模型组和氟西汀组大鼠随机给予不可预知性轻度刺激11周,制备抑郁症模型。氟西汀组于第7~11周灌胃氟西汀(10 mg·kg^(-1)·d^(-1)),其余组大鼠灌胃1 mL生理盐水。干预结束后进行行为学检测,酶联免疫吸附试验检测脑组织中白细胞介素(IL)-1β和IL-18的含量,免疫荧光染色观察海马CA3区和皮质区中NLRP3、凋亡相关斑点样蛋白(ASC)和胱天蛋白酶1(Caspase-1)的表达情况。Western blot测定脑组织TLR4、NF-κB、NLRP3、Caspase-1和活化的Caspase-1(cleaved Caspase-1)蛋白的表达水平。结果与模型组比较,氟西汀组大鼠在旷场的运动距离及站立次数显著增多,在高架十字迷宫的运动距离增加,且在闭臂的停留时间减少,大鼠脑组织中IL-1β和IL-18含量显著降低,TLR4、NF-κB、NLRP3、ASC、Caspase-1和cleaved Caspase-1蛋白的表达降低(P<0.05)。结论氟西汀可能通过抑制TLR4/NF-κB/NLRP3炎症体信号通路,降低脑组织中炎性因子IL-1β和IL-18的水平,从而改善CUMS大鼠的抑郁样行为。
Objective To investigate the effects of fluoxetine on depression-like behavior in chronic unpredictable mild stress(CUMS) model rats based on Toll-like receptor 4(TLR4)/nuclear factor κB(NF-κB)/NOD-like receptor pyrin domain-associated protein 3(NLRP3) inflammasome signaling pathway.Methods Eighteen SD rats were randomly divided into the control group,the model group and the fluoxetine group.Rats in the model group and the fluoxetine group were randomly given CUMS for 11 weeks to establish depression model.The fluoxetine group was treated with fluoxetine(10 mg·kg^(-1)·d^(-1)) through gastric perfusion from the 7th to the 11th week,and the other groups were given 1 mL of normal saline by gavage.Behavioral tests were conducted after the intervention.The levels of interleukin(IL)-1β and IL-18 in brain tissue were tested by enzyme-linked immunosorbent assay(ELISA).The expression of NLRP3 protein,apoptosis-associated specklike protein(ASC) and cysteine aspartate protease 1(Caspase-1) protein in hippocampal CA3 area and cortical area regions were observed by immunofluorescence staining.Western blot assay was used to detect the protein expression levels of TLR4,NF-κB,NLRP3,Caspase-1 and activated cysteine aspartate protease 1(cleaved Caspase-1) in brain tissue.Results Compared with the model group,the movement distance and standing times of rats in open field test were significantly increased,the movement distance in the elevated plus maze test was increased,and the dwell time in closed arms was decreased in the fluoxetine group.The contents of IL-1β and IL-18 in brain tissue were significantly decreased,and expression levels of TLR4,NF-κB,NLRP3,ASC,Caspase-1 and cleaved Caspase-1 proteins were also down-regulated in the fluoxetine group than those of the model group(P <0.05).Conclusion Fluoxetine may improve depression-like behavior in CUMS rats by inhibiting TLR4/NF-κB/NLRP3 inflammasome signaling pathway and reducing the levels of inflammatory factors IL-1β and IL-18 in brain tissue.
作者
吕霞
黄丽
张美琳
樊珺婷
马泽微
刘欢
LYU Xia;HUANG Li;ZHANG Meilin;FAN Junting;MA Zewei;LIU Huan(Department of Nutrition and Food Science,School of Public Health,Tianjin Medical University,Tianjin Key Laboratory of Environment,Nutrition,and Public Health,Center for International Collaborative Research on Environment,Nutrition and Public Health,Tianjin 300070,China)
出处
《天津医药》
CAS
北大核心
2023年第2期160-165,共6页
Tianjin Medical Journal
基金
国家自然科学基金资助项目(82173516)。
