姜黄素对APP/PS1双转基因小鼠海马CA1区AKT及p-AKT表达的影响  

Effect of curcumin on expression of AKT and p-AKT in hippocampus CA1 area of APP /PS1 double transgenic mice

作　　者：党惠子[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]北京中医药大学东直门医院中医内科学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)

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.

关 键 词：姜黄素 APP PS1双转基因小鼠 丝 苏氨酸激酶 磷酸化的丝 苏氨酸激酶 

分 类 号：R285.5[医药卫生—中药学]