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姜黄素对APP/PS1双转基因小鼠海马PI3K及p-PI3K表达的影响
引用本文:党惠子,李瑞晟,王虹,任映,孙海芸,杨金铎,王蓬文.姜黄素对APP/PS1双转基因小鼠海马PI3K及p-PI3K表达的影响[J].中国中药杂志,2013,38(9):1295-1299.
作者姓名:党惠子  李瑞晟  王虹  任映  孙海芸  杨金铎  王蓬文
作者单位: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;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
2. 新疆医科大学第二附属医院,新疆乌鲁木齐,830028
3. 北京美中宜和妇儿医院,北京,100016
基金项目: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双转基因小鼠磷酯酰肌醇-3激酶(phosphatidylinositol-3-kinase,PI3K)和磷酸化磷酯酰肌醇-3激酶(phosphorylated phosphatidylinositol-3-kinase,p-PI3K)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、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),对照组为同月龄同背景的非转基因小鼠.连续灌胃3个月后,应用免疫组织化学和Western blot方法检测小鼠海马中PI3K和p-PI3K的蛋白表达.结果:免疫组化染色模型组小鼠大脑海马CA1区PI3K和p-PI3K阳性细胞均较对照组明显减少(P<0.05);与模型组相比,各干预组PI3K及p-PI3K阳性细胞均有不同程度的增加,而以罗格列酮组与姜黄素中剂量组阳性细胞恢复最为显著(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APP/PS1双转基因小鼠海马中已减少的PI3K和p-PI3K蛋白有所恢复,提示姜黄素可能通过调节PI3K途径的胰岛素信号转导通路发挥抗AD作用.

关 键 词:姜黄素  APP/PS1双转基因小鼠  磷酯酰肌醇-3激酶  磷酸化磷酯酰肌醇-3激酶
收稿时间:2013/1/29 0:00:00

Effects of curcumin on expression of PI3K and p-PI3K in hippocampus of AD mice
DANG Hui-zi,LI Rui-sheng,WANG Hong,REN Ying,SUN Hai-yun,YANG Jin-duo and WANG Peng-wen.Effects of curcumin on expression of PI3K and p-PI3K in hippocampus of AD mice[J].China Journal of Chinese Materia Medica,2013,38(9):1295-1299.
Authors:DANG Hui-zi  LI Rui-sheng  WANG Hong  REN Ying  SUN Hai-yun  YANG Jin-duo and WANG Peng-wen
Institution:Key Laboratory of Pharmacology of Dongzhimen Hospital, Beijing University of Chinese Medicine, State Administration of Traditional Chinese Medicine, Beijing 100700, China;Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China;The Second Hospital Affiliated to Xinjiang Medical University, Urumqi 830028, China;Amcare Women and Children's Hospital, Beijing 100016, China;Key Laboratory of Pharmacology of Dongzhimen Hospital, Beijing University of Chinese Medicine, State Administration of Traditional Chinese Medicine, Beijing 100700, China;Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China;Key Laboratory of Pharmacology of Dongzhimen Hospital, Beijing University of Chinese Medicine, State Administration of Traditional Chinese Medicine, Beijing 100700, China;Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China;Key Laboratory of Pharmacology of Dongzhimen Hospital, Beijing University of Chinese Medicine, State Administration of Traditional Chinese Medicine, Beijing 100700, China;Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China;Key Laboratory of Pharmacology of Dongzhimen Hospital, Beijing University of Chinese Medicine, State Administration of Traditional Chinese Medicine, Beijing 100700, China;Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
Abstract:Objective: To observe the effect of curcumin on the expression of PI3K (phosphatidylinositol-3-kinase, PI3K) and p-PI3K (phosphated phosphatidylinositol-3-kinase, p-PI3K) in the hippocampus of Alzheimer's disease (AD) model (APP/PS1 double transgenic) mice.Method: A total of 60 three-month-old APP/PS1 double transgenic mice were randomly divided into model group, rosiglitazone group (10 mg·kg-1·d-1) and curcumin large(400 mg·kg-1·d-1), medium(200 mg·kg-1·d-1) and small(100 mg·kg-1·d-1) dose group.Twelve C57BL/6J mice in the same age and genetic background as APP/PS1 double transgenic mice were used as normal control group.All the 6 groups of mice were intragastrically administered for 3 months.After 3 months, the expression of PI3K and p-PI3K were detected by immunohistochemistry and Western blot.Result: The expression of PI3K and p-PI3K positive cells in hippocampus CA1 region significantly decreased in model group compared with normal control group (P<0.05), while compared with model group, PI3K and p-PI3K positive cells of all the curcumin intervention groups increased to varying degrees in hippocampus CA1 region,especially the middle dose group(P<0.01).Besides,Western blot results of the curcumin high dose group were also increased obviously (P<0.05).Conclusion: Curcumin can recover the decreased PI3K and p-PI3K and improve the insulin-signaling transmission in the hippocampus of APP/PS1 double transgenic mice.The mechanism of curcumin maybe by regulating the insulin signal transduction to treat AD.
Keywords:curcumin  APP/PS1 double transgenic mice  PI3K  p-PI3K
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