姜黄素对APP/PS1双转基因小鼠海马组织中酵母自噬相关基因Beclin1表达和淀粉样蛋白生成的影响

Effects of curcumin on expression of yeast autophagy-associated Beclin1 gene and production of amyloid in hippocampus of APP / PS1 double transgenic mouse model

目的观察姜黄素(curcumin)对APP/PS1(β-amyloid precursop protein/presenilin-1)双转基因阿尔茨海默病(alzheimer disease,AD)模型小鼠大脑海马组织中自噬相关基因Beclin1的表达以及淀粉样蛋白β(β-amyloid,Aβ)42生成的影响。方法将APP/PS1双转基因小鼠随机分为姜黄素高、低剂量模型组和空白对照组,每组10只,高、低剂量组分别将姜黄素按1 000和160 mg/kg加入饲料中喂养,连续给药6个月,空白对照组给予正常饲料,采用免疫组化和Western blot法检测姜黄素对小鼠大脑海马中Beclin1的表达和Aβ42生成的作用。结果与空白对照组相比,高、低剂量模型组小鼠大脑海马中Beclin1蛋白阳性细胞数及表达量均明显增多(P均<0.05),Beclin1蛋白的表达无剂量依赖性;Aβ42的生成随药物浓度的增加明显减少(P<0.05)。结论姜黄素可诱导APP/PS1双转基因小鼠大脑海马组织中Beclin1蛋白的表达,其机制可能是姜黄素通过促进自噬作用而抑制了Aβ42的生成,从而发挥其保护作用。

Objective To observe the effects of curcumin on expression of yeast autophage-associated Beclinl gene and production of amyloid Aβ42 in the hippocampus of APP/PS1 double transgenic mouse model. Methods APP/PS1 dou-ble transgenic mice were randomly divided into two test and one control groups, ten for each. The mice in test groups 1 and 2 were fed with diet containing curcumin at dosages of 1 000 and 160 mg/kg respectively, while those in control group with normal diet. The expression of Beclinl and production of Aβ42 in hippocampus of mice were determined by immunohistochemical assay and Western blot respectiv ely. Results As compared with those in control group, both the Beclinl-positive cell counts and Beclinl expression levels in two test groups increased significantly （P 〈 0. 05）, while the expression level was not dose-dependent. However, the expression level of Aβ42 decreased significantly with the increas-ing dose of curcumin （P 〈 0. 05）. Conclusion Curcumin induced the expression of Beclinl in hippocampus of APP/ PS1 double transgenic mouse models, of which the mechanism might be that curcumin inhibited the production of Aβ42 by enhancing autophagy.