姜黄素对APP/PS1双转基因小鼠海马IRS-1和p-IRS-1表达的影响  

Effect of curcumin on hippocampal IRS-1 and p-IRS-1 expressions in APP/PS1 double transgenic mice

作　　者：冯慧利[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]北京中医药大学东直门医院中药药理学实验室国家中医药管理局三级实验室,北京100700 [2]北京中医药大学东直门医院中医内科教育部重点实验室和北京市重点实验室,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》2013年第9期1290-1294,共5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项目(IRT0810)

摘　　要：目的:观察姜黄素对AD模型APP/PS1双转基因小鼠胰岛素受体底物-1(insulin receptor substrate-1,IRS-1)和磷酸化胰岛素受体底物-1(p-IRS-1)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、阳性对照罗格列酮组(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、Western blot和RT-PCR方法进行检测。结果:IRS-1和p-IRS-1免疫组化染色,模型组小鼠大脑海马CA1区IRS-1阳性细胞较对照组明显增加(P<0.01),p-IRS-1明显减少(P<0.01);与模型组相比,姜黄素各干预组可减少IRS-1阳性细胞数(P<0.05或P<0.01),并升高p-IRS-1阳性细胞数(P<0.05或P<0.01)。Western blot检测海马IRS-1和p-IRS-1的蛋白表达结果与免疫组织化学检测结果一致。RT-PCR检测IRS-1 mRNA表达结果与免疫组织化学和Westernblot结果相反。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,并增加IRS-1 mR-NA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AD作用。Objective： To observe the effect of curcumin on the expressions of insuhn receptor substrate-1 （ IRS-1 ） and phos- phated insulin receptor substrate-1 （p-IRS-1） in APP/PS1 double transgenic mice of the AD model. Method： Three-month-old APP/ PSI double transgenic mice were randomly divided into the model group, the positive rosiglitazone control group and curcumin high （400 mg·kg^-1·d^-1 ）, medium （200 mg·kg^-1·d^-1 ） and low （ 100 mg·kg^-1·d^-1 ） dose groups. The normal group was com- posed of non-transgenic mice under the same background. After they were orally administered for three months, they were detected with immunohistochemistry, Western blot and RT-PCR. Result： According to IRS-1 and p-IRS-1 immumohistochemical staining, the ex- pression of IRS-1 positive cells in hippocampus CA1 area in model mice was significantly higher than that of the normal control group （ P 〈 0. 01 ）. Compared with the model group, the number of IRS-1 positive cells in hippocampus CA1 area decreased （ P 〈 0. 05 or P 〈 0. O1 ） and the number of p-IRS-1 positive cells in hippocampus CA1 area increased in all of curcumin intervention groups. West- ern blot results were consistent with IRS-1 and p-IRS-1 protein expressions and immunohistochemistry results. RT-PCR test showed op- posite IRS-1 mRNA expression results with immunohistochemistry and Western blot results. Conclusion： Curcumin can recover in- creased IRS-1 and decreased p-IRS-1 in hippocampus of APP/PS1 double transgenic mice, increase IRS-1 mRNA expression, and im- prove the insulin-signaling transduction in APP/PS1 double transgenic mice. This suggests that curcumin can regulate the insulin-signa- ling transduction mechanism and show an anti-AD effect.

关 键 词：姜黄素 APP PS1双转基因小鼠 胰岛素受体 胰岛素样受体底物 

分 类 号：R285.5[医药卫生—中药学]