姜黄素对APP/PS1双转基因小鼠学习记忆及海马炎症信号通路的影响

The effect of curcumin on learning-memory ability and inflammatory signaling pathway in hippocampus of APP/PS1 double transgenic mice

目的:探讨喂饲姜黄素对淀粉样前体蛋白/早老素1(APP/PS1)双转基因小鼠学习记忆和海马β-淀粉样蛋白(Aβ)含量及高迁移率族蛋白1(HMGB1)、晚期糖基化终产物受体(RAGE)、Toll样受体4(TLR4)、核转录因子-κB(NF-κB)p65表达的影响。方法:20只雄性转基因小鼠随机分为模型组(M组,n=10)和治疗组(T组,n=10),另选10只雄性同窝野生型小鼠作为对照组(C组,n=10)。T组4月龄起喂饲含姜黄素(100mg·kg-1·d-1)的饲料,M组和C组喂饲普通饲料,9月龄时进行Morris水迷宫实验,免疫组织化学和Westernblot分别检测Aβ和HMGB1、RAGE、TLR4、NF-κBp65蛋白的表达。结果:与C组比,M组水迷宫实验中逃避潜伏期延长(P<0.05),且平均跨平台次数减少(P<0.05),海马CA1区和DG区Aβ数量及IOD值增加(P<0.05),海马中HMGB1、RAGE、TLR4和NF-κBp65表达均增多(P<0.05)。与M组比,T组逃避潜伏期缩短(P<0.05),且平均跨平台次数增多,海马CA1区和DG区Aβ数量及IOD值降低(P<0.05),海马中HMGB1、RAGE、TLR4和NF-κBp65表达均减少(P<0.05)。结论:持续喂饲姜黄素5个月可显著改善APP/PS1双转基因小鼠的学习记忆能力并减少海马Aβ含量,其机制可能与抑制海马HMGB1-RAGE/TLR4-NF-κB信号通路有关。

Objective:To investigate the effect of feeding curcumin on learning and memory ability,amyloid-β(Aβ)and the protein expression of high mobility group box protein-1(HMGB1),receptor for advanced glycation endproducts(RAGE),Toll-like receptors 4(TLR4),nuclear factor kappa B(NF-κB)p65 in the hippocampus of amyloid precursor protein/presenilin 1(APP/PS1)double transgenic mice.Methods:Male transgenic mice(n=20)were randomly divided into model group(M group,n=10)and treatment group(T group,n=10),the littermate wild-type male mice(n=10)were used as control(C group,n=10).The 4-month-old mice in T group were fed with curcumin diet(100 mg.kg-1.d-1),M group and C group were fed with normal diet.Morris water maze was applied to test the learning and memory ability for all 9-month-old mice.Aβand the protein expression of HMGB1,RAGE,TLR4,NF-κB p65 in the hippocampus were determined by immunohistochemistry and Western blot respectively.Results:Compared with group C,the mice in group M had longer escape latencies(P<0.05)and the average number across platform was decreased(P<0.05)in Morris water maze test,the number of Aβand the value of IOD was increased in CA1 region and DG region of hippocampus(P<0.05),while the protein expression of HMGB1,RAGE,TLR4,NF-κB p65(P<0.05)was significantly increased.Compared with group M,the mice in group T had shorter escape latencies(P<0.05)and the average number across platform was increased(P<0.05),the number of Aβand the value of IOD were decreased in CA1 region and DG region of hippocampus(P<0.05),the protein expression of HMGB1,RAGE,TLR4,NF-κB p65 was significantly increased(P<0.05).Conclusion:Oral curcumin for 5 months reverses the learning and memory impairment of APP/PS1 transgenic mice,and the mechanism is likely to inhibit HMGB1-RAGE/TLR4-NF-κB signaling pathway.