中国中药杂志

2012, v.37(06) 836-841

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还脑益聪方提取物对不同月龄APP转基因小鼠行为学及其海马区线粒体超微结构的影响
Effects of Huannao Yicong formula extract on behavior and ultrastructure of hippocampus mitochondria of APP transgenic mice of different months

刘明芳;李浩;刘剑刚;刘龙涛;官杰;蔡琳琳;胡佳;魏芸;
LIU Mingfang1,LI Hao1,LIU Jian′gang1,LIU Longtao1,GUAN Jie2,CAI Linlin1,HU Jia3,WEI Yun3(1.Geratology Center of Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China; 2.Endocrine Department of Qingdao Haici Medical Group of Shandong Provience,Qingdao 266033,China; 3.National Key Laboratory of Chemical Resource Engineering of Beijing University of Chemical Technology,Beijing 100029,China)

摘要(Abstract):

目的:研究还脑益聪方提取物对不同月龄APP转基因小鼠行为学及其海马CA1区线粒体超微结构的影响,从能量代谢的角度探讨中药提取物治疗AD的部分作用机制。方法:选用3月龄APP695V717I转基因小鼠120只为痴呆模型,随机分为模型组、盐酸多奈哌齐组、还脑益聪方提取物高剂量组、低剂量组,每组30只,并设正常对照组。采用Morris水迷宫及跳台实验观察试验动物的行为学;应用透射电镜观察模型脑海马区线粒体超微结构。结果:7,9月龄APP转基因模型小鼠Morris水迷宫试验中穿越原平台位置次数、游泳时间和路程均较转基因模型组显著增多(P<0.05,P<0.01)、跳台实验中的潜伏期均明显缩短(P<0.01),且随着病程的进展而有加重之势。还脑益聪方提取物能明显提高不同月龄转基因小鼠穿越原平台位置次数、游泳时间和路程(P<0.05,P<0.01),且明显延长跳台实验中的潜伏期(P<0.05,P<0.01)。7,9月龄APP转基因小鼠海马CA1区神经元线粒体均表现出线粒体膜破坏、溶解,内嵴大部分排列轻度紊乱,有的嵴内腔扩张,基质疏松,线粒体肿胀,且随病程进展而损坏加重;还脑益聪方提取物能改善不同月龄APP转基因小鼠海马CA1区线粒体超微结构与数量。结论:APP转基因小鼠AD模型学习记忆能力显著下降,且该模型海马CA1区神经元线粒体数量减少、结构损伤,且随病程进展而均显加剧;还脑益聪方提取物能够改善不同病程APP转基因小鼠的学习记忆能力,其可能与改善海马区神经元线粒体结构、增加线粒体数量而保护脑功能有关。
Objective: To study the effects of Huannao Yicong formula(HNYCF) extract on behavior and ultrastructure of mitochondria in hippocampus CA1 area of APP transgenic mice of different months,and explore its partial mechanism in treating Alzheimer′s disease(AD) through the perspective of energy metabolism.Method: One hundred and twenty APP695V717I transgenic mice of 3-month old were divided randomly into model group,Donepezil group(0.65×10-3 g·kg-1·d-1),HNYCF extract large dose group(2.8 g·kg-1·d-1) and HNYCF extract small dose group(1.4 g·kg-1·d-1),and 30 mice in each group.Another 30 C57BL/6J mice with the same age and background were used as normal control group.All animals were administered once daily by gavage with the corresponding drug or distilled water.The course of intervention was 4 and 6 months.Behavioral changes were observed by Morris water maze test and step down test.Ultrastructure of mitochondria in hippocampus CA1 area was observed by transmission electron microscope.Result: At the age of 7 and 9 month,the number of times of passing through platform,swimming time and path length of model group increased significantly(P<0.05,P<0.01) in Morris water maze test,and the latent period decreased(P<0.01)in step down test compared with normal group,and it would get worse with the development of disease course.HNYCF extract could increase the number of times of passing through platform,swimming time and path length(P<0.05,P<0.01) in Morris water maze test,prolong latent period in step down test of different age.At the age of 7 and 9 month,mitochondrial of hippocampus CA1 area was disrupted and dissolved.Most ridge structure arranged in a mess,and some ridge showed expanding,matrix loosing and swollen appearance,and it would get worse with the development of disease course.HNYCF extract could improve ultrastructure of mitochondria in hippocampus CA1 area,and increase its quality.Conclusion: Learning and memory ability decreased in APP transgenic mice model,and the quantity of neural mitochondria in hippocampus CA1 area with structure disrupting,and it would get worse with the development of disease course.HNYCF extract could improve the learning and memory ability of APP transgenic mice model,its mechanism might relate with improving ultrastructure of mitochondria in hippocampus,and increasing its quantity.

关键词(KeyWords): 还脑益聪方提取物;APP转基因小鼠;行为学;海马;线粒体超微结构;能量代谢
HNYCF extract;mitochondria;hippocampus;behavior;ultrastructure;APP transgenic mice;energy metabolism

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(30873338,81173383);; 国家“重大新药创制”科技重大专项(2009ZX09103-391)

作者(Author): 刘明芳;李浩;刘剑刚;刘龙涛;官杰;蔡琳琳;胡佳;魏芸;
LIU Mingfang1,LI Hao1,LIU Jian′gang1,LIU Longtao1,GUAN Jie2,CAI Linlin1,HU Jia3,WEI Yun3(1.Geratology Center of Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China; 2.Endocrine Department of Qingdao Haici Medical Group of Shandong Provience,Qingdao 266033,China; 3.National Key Laboratory of Chemical Resource Engineering of Beijing University of Chemical Technology,Beijing 100029,China)

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