摘要
目的:观察姜黄素对AD模型APP/PS1双转基因小鼠丝/苏氨酸激酶(serine-threonine kinase,AKT,又称PKB)和磷酸化的丝/苏氨酸激酶(phosphorylated serine-threonine kinase,即p-AKT)表达的影响。方法:将3月龄的APP/PS1双转基因小鼠随机分为5组,分别为模型组、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),选取同月龄同背景的非转基因小鼠为对照组。连续灌胃3个月后,应用免疫组织化学和Western blot方法检测小鼠海马CA1区中AKT和p-AKT的蛋白表达。结果:免疫组化染色,模型组小鼠大脑海马CA1区AKT和p-AKT阳性细胞均较对照组明显减少(P<0.05,P<0.01),与模型组相比,罗格列酮组与姜黄素高、中剂量组AKT和p-AKT阳性细胞均有明显恢复(P<0.05,P<0.01),其中姜黄素中剂量组p-AKT阳性细胞数增加最为显著(P<0.01)。Western blot检测结果与免疫组化结果基本一致。结论:姜黄素可以使AD模型APP/PS1双转基因小鼠海马CA1区中减少的AKT和p-AKT细胞有所恢复,提示姜黄素可能通过调节AKT及其磷酸化过程,从而进一步调节PI3K/AKT途径的胰岛素信号转导通路发挥抗AD作用。
Objective： To observe the effect of curcumin on the expressions of AKT （serine-threonine kinase, AKT, also known as PKB） and p-AKT （phosphated serine-threonine kinase, p-AKT） 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 rosiglitazone （10 mg· kg-1 · d-1） group, and high （400 mg· kg-1 · d-1） , medium （200 mg· kg-1 · d-1） and low （100mg· kg-1 · d-1） dose curcu- min groups. Non-transgenic mice of the same age and background were selected as the control group （n = 12）. After all of the six groups were intragastrically administered for consecutively three months, the protein expressions of AKT and p-AKT in hippocampus CA1 area were detected by immunohistochemistry and Western blot. Result： The results of immunohistochemistry showed that the ex- pression of AKT and p-AKT positive cells in hippocampus CA1 area significantly decreased in the model group （P 〈 0. 05 and P 〈 0. 01 ）. Compared with the model group, AKT and p-AKT positive cells of hippocampus CA1 area increased obviously in the rosiglita- zone group and high and medium dose curcumin group （P 〈 0. 05 or P 〈 0. 01 ）, especially the medium dose group （P 〈 0. 01 ）. The results of Western blot were consistent with that of immunohistochemistry. Conclusion： Curcumin can recover the decreased AKT and p-AKT cells in hippocampus CA1 area of APP/PS1 double transgenic mice of the AD model, suggesting that curcumin may regulate AKT and its phosphorylation process, as well as PI3K/AKT insulin signal transduction pathway, and show the anti-AD effect.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2013年第19期3327-3331,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(IRT0810)
作者简介
党惠子，博士研究生，E—mail：danghz@163．com
[通信作者]王蓬文，博士，教授，博士生导师，Tel：（010）84013195
