姜黄素对AD双转基因小鼠的Aβ产生神经保护作用的影响  

Neuroprotective effect of curcumin to Aβ of double transgenic mice with Alzheimer's disease

作　　者：冯慧利[1] 樊惠[1] 党惠子[1] 陈晓培[1] 任映[1] 杨金铎[1] 王蓬文[1] 

机构地区：[1]国家中医药管理局三级实验室中医内科学教育部重点实验室和北京市重点实验室北京中医药大学东直门医院中药药理学实验室,北京100700

出　　处：《中国中药杂志》2014年第19期3846-3849,共4页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(81073076);教育部高等学校创新团队(IRT0810)

摘　　要：目的:观察姜黄素对3月龄APPswe/PS1d E9双转基因小鼠干预6个月脑内Aβ40,Aβ42和Aβ42寡聚体-ADDLs的变化,探讨姜黄素的神经保护作用。方法:将APPswe/PS1d E9双转基因小鼠随机分为模型组、罗格列酮组(10 mg·kg-1·d-1)和姜黄素高、中、低剂量组(400,200,100 mg·kg-1·d-1),正常对照组采用的是同月龄同背景的C57/BL6J小鼠,于3月龄开始连续灌胃6个月,运用免疫组织化学方法和Western blot方法观察小鼠海马CA1区Aβ40,Aβ42和ADDLs的阳性细胞及分布和蛋白表达的变化。结果:免疫组织化学和Western blot方法均观察到模型组小鼠海马CA1区Aβ40,Aβ42和ADDLs阳性细胞数和蛋白表达均较对照组增加(P<0.01)。与模型组相比,免疫组化结果罗格列酮组与模型组相比均降低(P<0.05),Western blot见显著减低(P<0.01);姜黄素高剂量组Aβ40,Aβ42和ADDLs阳性细胞数和蛋白表达均减少,中剂量组显著减少(P<0.01),低剂量组Aβ40和Aβ42蛋白表达也减少。结论:姜黄素连续干预6个月仍可以显著减少APPswe/PS1d E9双转基因小鼠脑内海马Aβ40,Aβ42和ADDLs的表达,姜黄素是否可以通过下调Aβ40,Aβ42和ADDLs的表达,影响Aβ级联反应,从而发挥神经保护,还需要更深入的研究。Objective： To observe the changes in Aβ40, Aβ42 and ADDLs in brains of 3 month-old APPswe/PSldE9 double transgenic mice after six-month intervention with curcumin, in order to discuss the neuroprotective effect of curcumin. Method： APP- swe/PSldE9dtg mice were randomly divided into the model group, the Rosiglitazone group （10 mg · kg^-1 · d^-1） and curcumin high （400 mg · kg^-1 · d^-1 ）, medium （200 mg · kg^-1 · d^-1 ） and low （100 mg · kg^-1 · d^-1 ） dosage groups, with C57/BL6J mice of the same age and the same background in the normal control group. After 6 months, the immunohistochemical staining （IHC） and the Western blot method were used to observe the changes in positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area, their distribution and protein expressions. Result： Both of the immunohistochemical staining and the Western blot method showed more positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area and higher protein expressions in the model group than the normal group （ P 〈 0. 01 ）. IHC showed a lower result in the Rosiglitazone group than the model group （ P 〈 0. 05 ）, while Western blot showed a much lower result （P 〈 0. 01 ）. The number of Aβ40, Aβ42 and ADDLs positive cells and the protein expressions decreased in the curcumin high group, the medium group showed a significant decrease （P 〈 0. 01 ）, and the low dose group also showed reductions in the protein expressions of Aβ40 and Aβ42. Conclusion： The six-month intervention with curcumin can significantly reduce the expressions of hippocampal Aβ40, Aβ42 and ADDLs in brains of APPswe/PS1 dE9 double transgenic mice. Whether curcumin can impact Aft cascade reaction by down-regnlating expressions of Aβ40, Aβ42and ADDLs and show the neuroprotective effect needs further studies.

关 键 词：阿尔茨海默病 姜黄素 APPswe/PS1dE9双转基因小鼠 Aβ级联反应 

分 类 号：R285.5[医药卫生—中药学]