穿心莲内酯抑制IKK/IκBα/NF-κB信号通路改善抑郁症大鼠的抑郁样行为  

Andrographolide improves depressive behaviors in rats with major depressive disorder by inhibiting the inhibitor of kappa B kinase/nuclear factorκB inhibiting proteinα/nuclear factor-κB signaling pathway

作　　者：赵雯婧 王婷婷 邱雪 蔡晓 简薇[1] 何宗岭[3] 郑玉萍 ZHAO Wenjing;WANG Tingting;QIU Xue(Department of Geriatric Psychiatry,the Fourth People’s Hospital of Chengdu,Sichuan,Chengdu 610036,China;不详)

机构地区：[1]四川省成都市第四人民医院老年精神科,610036 [2]四川省成都市第四人民医院急性精神科,610036 [3]四川省成都市第四人民医院临床心理科,610036 [4]四川省成都市第八人民医院老年科

出　　处：《河北医药》2023年第14期2085-2089,共5页Hebei Medical Journal

基　　金：国家自然科学基金资助项目(编号:62173069)。

摘　　要：目的探讨穿心莲内酯(Andro)通过抑制核转录因子-κB抑制蛋白激酶(IKK)/核因子κB抑制蛋白(IκBα)/核因子-κB(NF-κB)信号通路改善抑郁症(MDD)大鼠的抑郁样行为。方法随机取12只SD大鼠作为空白对照组(NC组),其余大鼠采用慢性不可预知轻度应激(CUMS)结合孤养模式造模,将造模成功大鼠随机平分为模型组(Mod组)、Andro组(25 mg·kg^(-1)·d^(-1))、Res组(30 mg·kg^(-1)·d^(-1)IKK/IκBα/NF-κB信号通路激活剂Res)、Andro+Res组(25 mg·kg^(-1)·d^(-1)Andro+30mg·kg^(-1)·d^(-1)Res),每组12只大鼠,Mod组和NC组灌胃等量0.9%氯化钠溶液。旷场实验、糖水偏好实验、强迫游泳实验、平衡木实验评估大鼠行为;ELISA法检测血清IL-1β、IL-6、TNF-α水平;免疫荧光染色检测小胶质细胞、星形胶质细胞活性;Western blot检测NLRP3、cleaved-Caspase-1以及IKK/IκBα/NF-κB信号通路蛋白水平。结果与NC组相比,Mod组站立次数、饮用蔗糖量显著减少(P<0.05),游泳不动时间、通过平衡木时间、IL-1β、IL-6、TNF-α含量、Iba-1、GFAP阳性细胞数量、NLRP3、cleaved-Caspase-1、p-IKK/IKK、IκBα、p-NF-κB p65/NF-κB p65蛋白水平显著增加(P<0.05);与Mod组相比,Andro组大鼠游泳不动时间、通过平衡木时间、IL-1β、IL-6、TNF-α含量、Iba-1、GFAP阳性细胞数量、NLRP3、cleaved-Caspase-1、p-IKK/IKK、IκBα、p-NF-κB p65/NF-κB p65蛋白水平显著降低(P<0.05),站立次数、饮用蔗糖量显著增加(P<0.05),而Res组以上指标趋势相反(P<0.05);Res逆转了Andro对MDD大鼠抑郁样行为的改善。结论Andro可能通过下调IKK/IκBα/NF-κB通路对MDD大鼠的抑郁样行为起到一定的改善作用。Objective To investigate the effect of andrographolide(Andro)on alleviating depressive behaviors in rats with major depressive disorder(MDD)by inhibiting the nuclear transcription factor-inhibitor of kappa B kinase(IKK)/nuclear factorκB inhibiting proteinα(IκBα)/nuclear factor-κB(NF-κB)signaling pathway.Methods Twelve SD rats were randomly selected as the blank control group(NC group),and the rat MDD model was created by chronic unpredictable mild stress(CUMS)combined with orphanage.MDD rats were randomly divided into model group(Mod group),Andro group(treatment of Andro 25mg·kg^(-1)·d^(-1)),Res group(treatment of IKK/IκBα/NF-κB signal pathway activator Res 30mg·kg^(-1)·d^(-1)),and Andro+Res group(Andro 25mg·kg-1·d+Res 30mg·kg^(-1)·d^(-1)),with 12 rats in each group.Rats in Mod group and NC group were given the same amount of normal saline by oral gavage.Open field experiment,sugar preference experiment,forced swimming experiment,and balance beam experiment were used to evaluate the behaviors of rats.ELISA was used to detect serum levels of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α).Immunofluorescence staining was used to detect the activities of microglia and astrocytes.Western blot was used to detect the protein levels of Nod-like receptor protein 3(NLRP3),cleaved Caspase-1 and proteins in the IKK/IκBα/NF-κB signaling pathway.Results Compared with those of NC group,the standing times and sugar consumption in Mod group significantly decreased(P<0.05).The swimming immobility time,balance beam passing time,serum levels of IL-1β,IL-6,and TNF-α,the numbers of ionised calcium-binding adapter molecule 1(Iba1)and glial fibrillary acidic protein(GFAP)positive cells,and the protein levels of NLRP3,cleaved Caspase-1,p-IKK/IKK,IκBα,p-NF-κB p65/NF-κB p65 significantly increased in Mod group compared with those in NC group(P<0.05),which,in Andro group were significantly lower than those in Mod group(P<0.05).The standing times and sugar consumption in Andro group were significa

关 键 词：穿心莲内酯 抑郁症 IKK/IκBα/NF-κB信号通路 抑郁样行为 神经炎症 

分 类 号：R749.41[医药卫生—神经病学与精神病学]