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作 者:任映[1,2] 李瑞晟[3] 王虹[4] 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,北京100700 [2]北京中医药大学教育部重点实验室 [3]新疆医科大学第二附属医院 [4]北京美中宜和妇儿医院
出 处:《北京中医药大学学报》2012年第10期679-682,I0002,共5页Journal of Beijing University of Traditional Chinese Medicine
基 金:国家自然科学基金面上资助项目(No.81073076);北京市自然科学基金面上资助项目(No.7092057)
摘 要:目的观察淀粉样前体蛋白/早老素1(APP/PS1)双转基因小鼠海马CA1区神经元胆碱乙酰转移酶(ChAT)表达,评价姜黄素对APP/PS1双转基因小鼠学习记忆的影响。方法将3月龄的APP/PS1双转基因小鼠随机分为模型组、罗格列酮组及姜黄素大、中、小剂量组,并以同月龄遗传背景相同的C57BL/6J小鼠作为正常对照组。各治疗组每天灌胃给药1次,连续灌胃3个月。应用跳台实验、免疫组织化学和蛋白质印迹(Western-blot)检测学习记忆能力和海马神经元ChAT的变化。结果与正常组小鼠相比,模型组小鼠潜伏时间显著缩短(P<0.01),与模型组小鼠相比,姜黄素各剂量组小鼠潜伏时间增加(P<0.05或P<0.01)。免疫组化检测,模型组小鼠海马CA1区ChAT阳性细胞较正常对照组明显减少(P<0.01),而姜黄素干预组可以使其不同程度地恢复。Western blot检测,模型组小鼠海马ChAT的蛋白表达条带比正常组小鼠明显变细、颜色变浅(P<0.01);姜黄素干预组小鼠海马ChAT的蛋白表达条带均明显增粗、颜色加深(P<0.05或P<0.01)。结论姜黄素能通过增加ChAT的蛋白表达,促进阿尔茨海默(AD)模型动物神经传导障碍,进而改善APP/PS1双转基因小鼠的学习记忆能力。Objective To observe the expression of neuron choline acetyl-transferase (CHAT) in hippocampus CA1 zone in APP/PS1 double transgenic mice, and review the influence of curcumin on learning and memory ability. Methods All APP/PS1 double transgenic mice (3 months old) were randomly divided into model group, rosiglitazone group, and high-dose, mid-dose and low-dose curcumin group (high-dose group, mid-dose group and low-dose group), and C57BL/6J mice with the same age and genetic background were assigned into normal group. All groups were intragastrically given relevant medicinal respectively once a day for 3 months. The changes of learning and memory ability and hippocampus neuron ChAT were detected by using platform experiment, immunohistochemistry technique and Western blot method. Results Compared with normal group, latency time was much shorter inmodel group (P 〈 0.01 ). Compared with control group, latency time was much longer in all curcumin groups ( P 〈 0.05 or P 〈 0.01 ). The results of immunohistochemistry technique showed that ChAT positive cells in hippocampus CA1 zone decreased significantly in model group compared with normal group (P 〈 0.01 ), and recovered in varying degrees in all curcumin groups. The results of Western blot method showed that the protein strips of ChAT became thinner and the color became paler in model group (P 〈 0.01 ), and became thicker and became darker ( P 〈 0.05 or P 〈 0.01 ) in all curcumin groups. Conclusion Curcumin can improve learning and memory ability in APP/PS1 double transgenic mice through improving the protein expression of ChAT and alleviate the disorder of neural conduction in animal model of Alzheimer' s Disease.
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