姜黄素对APP/PS1双转基因小鼠突触相关蛋白表达的影响  

Effect of curcumin on synapse-related protein expression of APP/PS1 double transgenic mice

作　　者：魏鹏[1,2] 李瑞晟[3] 王虹[4] 任映[1,2] 孙海芸[1,2] 杨金铎[1,2] 王蓬文[1,2] 

机构地区：[1]国家中医药管理局三级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 [2]北京中医药大学教育部重点实验室,北京100700 [3]新疆医科大学第二附属医院,新疆乌鲁木齐830028 [4]北京美中宜和妇儿医院,北京100016

出　　处：《中国中药杂志》2012年第12期1818-1821,共4页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(81073076);北京市自然科学基金面上项目(7092057);高等学校学科创新引智基地(111计划)教育部和国家外国专家局[B08006]项目

摘　　要：目的:观察姜黄素对AD模型APP/PS1双转基因小鼠突触相关蛋白突触后致密蛋白-95(postsynaptic densityprotein-95,PSD-95)和骨架蛋白Shank1表达的影响。方法:将3月龄的APP/PS1双转基因小鼠随机分为模型组、罗格列酮阳性对照组(10 mg.kg-1.d-1)、姜黄素高、中、低剂量组(400,200,100 mg.kg-1.d-1),正常对照组为相同背景非转基因小鼠。灌胃3个月后,应用免疫组织化学和Western blot方法进行检测。结果:行为学检测,治疗组与模型组相比定位航行实验和空间探索实验存在不同程度的差异(P<0.01或P<0.05)。PSD-95和Shank1免疫组化,模型组小鼠大脑海马CA1区较对照组阳性细胞明显减少(P<0.01),姜黄素干预组有所恢复。Western blot检测海马PSD-95的蛋白结果显示,模型组小鼠海马PSD-95的蛋白表达条带均比对照组小鼠明显变细、颜色变浅(P<0.01);姜黄素干预组小鼠海马PSD-95的蛋白表达条带均明显增粗、颜色加深(P<0.05)。结论:姜黄素增加APP/PS1双转基因小鼠突触相关蛋白shank1和PSD-95表达,改善APP/PS1双转基因小鼠突触的结构和可塑性,提高空间学习记忆能力。Objective： To observe the effect of curcumin on the expression of synapse-related proteins PSD-95 and Shankl in APP/PS1 double transgenic mice. Method： Three-month-old APP/PS1 dtg mice were randomly divided into the model group, the pos- itive Rosiglitazone control group and curcumin high （400 mg ·kg·d^-1）, medium （200 mg ·kg·d^-1） and low （100 mg·kg·d^-1 ） dose groups, with non-genetically modified mice with the same background as the normal group. After the oral administration for three months, immunohistoehemistry and Western blot were adopted for detection. Result： According to the behavioral detection, the treatment group and the model group showed differences in the place navigation test and the spatial probe test to varying degrees （P 〈0. 01 or P 〈0. 05）. The expression of PSD-95 and Shankl-positive cells of hippocampus CA1 region significantly decreased in model mice compared with normal control group （P 〈 0. 01 ） ; while the curcumin intervention group showed recovery to some extend. Western blot results showed that the strap of PSD-95 protein expression became significantly thinner and lighter in the model group com- pared with the normal control group （ P 〈 0. 01 ） ; while the curcumin intervention group showed notably thicker and darker straps of PSD-95 protein expression （ P 〈 0. 05 ）. Conclusion ： Curcumin can increase the expression of synapse-related proteins PSD95 and Shankl in APP/PS1 double transgenic mice, improve structure and plasticity of synapse in APP/PS1 double transgenic mice and en- hance their learning and memory abilities.

关 键 词：姜黄素 APP/PS1双转基因小鼠 突触后致密蛋白-95 骨架蛋白Shank1 

分 类 号：R285.5[医药卫生—中药学]