姜黄素对阿尔茨海默病模型小鼠胰岛素受体底物-1的影响  

Effect of curcumin on expression of IRS-1 of double transgenic mice model with Alzheimer's disease

作　　者：党惠子[1] 魏鹏[1,2] 陈晓培[1,3] 任映[1] 杨金铎[1] 王蓬文[1] 

机构地区：[1]北京中医药大学东直门医院中药药理学实验室中医内科学教育部重点实验室北京市重点实验室,北京100700 [2]河南省焦作市中医院 [3]河南省开封市中医院

出　　处：《北京中医药大学学报》2015年第3期167-171,I0002,共6页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家自然科学基金面上资助项目(No.81073076);教育部和国家外国专家局项目(No.B08006)

摘　　要：目的观察姜黄素对阿尔茨海默病模型APP/PS1双转基因小鼠胰岛素受体底物-1(IRS-1)和磷酸化胰岛素受体底物-1(p-IRS-1)表达的影响,探讨姜黄素神经保护作用机制。方法将3月龄的APP/PS1双转基因小鼠随机分为模型组、罗格列酮组、姜黄素高(400 mg/kg)、中(200 mg/kg)、低(100 mg/kg)剂量组,并以同窝阴性小鼠作为正常对照组。连续灌胃6个月后,应用免疫组织化学、Western blot和RT-PCR法进行检测。结果免疫组化染色,模型组小鼠大脑海马CA1区IRS-1阳性细胞较正常组明显增加(P<0.01),与模型组相比,各干预组IRS-1阳性细胞数减少(P<0.05或P<0.01),p-IRS-1结果与IRS-1结果相反。Western blot检测海马IRS-1和p-IRS-1的蛋白表达结果与免疫组化检测结果一致。RT-PCR检测IRS-1 mRNA表达结果与免疫组化和Western blot结果一致。结论姜黄素可以使APP/PS1双转基因小鼠海马增加的IRS-1和减少的p-IRS-1得以恢复,并调节IRS-1mRNA表达,改善APP/PS1双转基因小鼠胰岛素信号转导,提示姜黄素可能通过调节胰岛素信号转导机制发挥抗阿尔茨海默病作用。Objective To observe the effect of curcumin on the expression of insulin receptor substrate-1 （ IRS-1 ） and phosphated insulin receptor substrate-I （ p-IRS-1 ） in the hippocampus of mice model with Alzheimer＇ s disease （AD）, so as to explore the mechanism of neuro-protective effect of curcumin. Methods Three-month-old APP/PS1 double transgenic mice were randomly divided into model group, rosiglitazone group（ 10 mg/kg） and high-, mid-, low- dose curcumin groups（high-dose group, mid-dose group, low-dose group）with the dose of 400,200 and 100 mg/kg （n =12 each）. Non-transgenic mice of the same brood were selected as control group. After intragastric administration for six consecutive months, the protein expressions of IRS-1 and p-IRS-1 in hippocampus CA1 area were detected by immunohistochemistry and Western blot, and the mRNA expression of IRS-1 were detected by RT-PCR. Results IRS-1 positive cells of hippocampus CA1 area significantly increased in model group than those of normal group （P 〈0.01 ）. Compared with model group, IRS-1 positive cells decreased（P 〈0.05 or P 〈0. 01 ）significantly in rosiglitazone group and three curcumin groups, while the expression of p-IRS-1 increased in all four intervention groups（P 〈 0.05 or P 〈 0.01 ）. Conclusion Curcumin can recover, to some extent, the protein contents of IRS-1 and p-IRS-1 in hippocampus CA1 area of APP/PS1 double transgenic mice. Furthermore, the expression of IRS-lmRNA can be down-regulated and insulin-signaling transmission of the APP/PS1 double transgenic mice can be improved. All these findings suggest that the potential mechanism of anti-AD effect of curcumin is by the way of regulating insulin signal transduction pathway.

关 键 词：姜黄素 阿尔茨海默病 双转基因小鼠 胰岛素受体底物-1 磷酸化胰岛素受体底物-1 IRS-1 p-IRS-1 

分 类 号：R285.5[医药卫生—中药学]