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

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(10mg.kg-1·d-1)、姜黄素高、中、低剂量组(400,200,l00mg.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).Westem blot检测海马IRS-I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Western blot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.

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

Objective: To observe the effect of curcumin on the expressions of insulin receptor substrate-1 (IRS-1) and phosphated insulin receptor substrate-1 (p-IRS-1) in APP/PS1 double transgenic mice of the AD model.Method: Three-month-old APP/PS1 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 composed 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 expression 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<0.01) and the number of p-IRS-1 positive cells in hippocampus CA1 area increased in all of curcumin intervention groups.Western blot results were consistent with IRS-1 and p-IRS-1 protein expressions and immunohistochemistry results.RT-PCR test showed opposite IRS-1 mRNA expression results with immunohistochemistry and Western blot results.Conclusion: Curcumin can recover increased IRS-1 and decreased p-IRS-1 in hippocampus of APP/PS1 double transgenic mice, increase IRS-1 mRNA expression, and improve the insulin-signaling transduction in APP/PS1 double transgenic mice.This suggests that curcumin can regulate the insulin-signaling transduction mechanism and show an anti-AD effect.