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

摘要

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(100 mg·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Western blot分别检测Aβ和HMGB1、RAGE、TLR4、NF-κB p65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-κB p65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-κB p65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 ad-vanced 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. Aβ and the protein ex-pression 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 Aβ and 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 Aβ and the value of IOD were decreased in CA1 region and DG region of hip-pocampus (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.