中药Ⅰ号方对APP/PS1双转基因AD小鼠模型行为和精神症状的影响  

Effects of a Chinese traditional prescription PN-1 on behavior and psychological symptoms in APP/PS1 transgenic mouse models of Alzheimer's disease

作　　者：姚志刚[1,2] 梁良[1,2] 刘羽[1,2] 王响[1,2] 朱华[1,2] 黄澜[1,2] 秦川[1,2] 

机构地区：[1]北京协和医学院比较医学中心 [2]中国医学科学院医学实验动物研究所卫生部人类疾病比较医学重点实验室国家中医药管理局人类疾病动物模型三级实验室,北京100021

出　　处：《中国实验动物学报》2012年第2期16-20,36,I0002,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：北京协和医学院2010年博士研究生创新基金项目(2010-1001-001)

摘　　要：目的研究中药I号方(PN-1)对APP/PS1双转基因AD小鼠模型行为和精神症状的影响。方法将5月龄的APP/PS1双转基因AD小鼠随机分为模型组(vehicle)、安理申(Aricept)治疗组(2 mg/kg)、PN-1低(0.6g/kg)、中(1.2 g/kg)、高(2.4 g/kg)剂量组,并以同窝阴性的C57BL/6小鼠作为正常对照组(WT),每组16只,雌雄各半。给药组小鼠每天灌胃给药1次,同时模型组及正常组小鼠给予等体积的双蒸水灌胃。给药前称量小鼠初始体重、摄食量和饮水量;给药期间,每两周逐只称量体重一次,同时称量并计算摄食量和饮水量。给药3个月后(8月龄)依次进行社会互动行为检测、旷场实验、Rota-rod实验和蔗糖饮水实验来观察PN-1对APP/PS1小鼠行为和精神症状的作用。结果给药期间,相同月龄下各组小鼠间的体重、摄食和饮水均无显著性差异(P>0.05)。社会互动行为检测发现PN-1显著减少模型小鼠异常增多的攻击、追逐和嗅闻次数(P<0.05)。旷场实验结果显示,PN-1能够减少转基因小鼠水平和垂直方向的运动(P<0.05)和高速运动时间(P<0.05),同时减少其进入中心区域的探究次数(P<0.05)并增加其修饰次数(P<0.05)。Rota-rod实验结果发现,PN-1能够增加转基因小鼠在滚轴上停留的时间(P<0.05)。蔗糖饮水实验结果显示,给予PN-1的转基因小鼠蔗糖偏嗜度有增高趋势,但与模型组相比并无显著性差异(P>0.05)。结论 PN-1能够改善APP/PS1双转基因小鼠的社会互动行为、减少过度增强的运动能力和探究行为,提高其耐力和平衡学习能力,并减轻其焦虑、烦躁、易激惹等精神症状。Objective To investigate the effects of a Chinese traditional prescription PN-1 on behavioral and psychological symptoms in APP/PS1 transgenic mouse models of Alzheimer＇s disease（AD）.Methods Mouse models at 5 months of age were randomly divided into model group（vehicle）,Aricept administration group（2 mg/kg）,PN-1 at low（0.6 g/kg）,middle（1.2 g/kg） and high（2.4 g/kg） doses.The wild-type littermates were chosen as normal control group（WT）.The 16 mice（8 males and 8 females） in each group were given once every day by intragastric administration of PN-1,Aricept or water for 3 months.The body weight and the amount of water drinking and food intakes were measured before administration and every two weeks during administration.After the drug administration,a battery of behavioral tests including social interaction,open field,rota-rod and sucrose preference were performed.Results During the administration,no changes in body weight and food/water intake were detected in PN-1-treated mice,compared with the age-matched wild-type control and vehicle mice（P 0.05）.Compared with the mice in the vehicle group,social interaction test showed reduced attack,chasing and sniffing in the PN-1-treated groups（P 0.05）.The mice in the PN-1-treated groups showed decreased spontaneous motor activity（P 0.05）,highly mobile duration（P 0.05）,frequency to center zone（P 0.05） and increased frequency of grooming in the open field test.Rota-rod test exhibited increased time spent on rod（P0.05） for the PN-1-treated mice.In addition,increased sucrose consumption was also found in the PN-1-treated group,however,no statistically significant difference was found compared with the vehicle group（P0.05）.Conclusions PN-1-treatment can ameliorate many non-cognitive behaviors and psychological symptoms in the APP/PS1 transgenic mouse models,including rescued hyperactive social interaction,spontaneous motor activity,improved ability to learn balance,and reduced anxiety,irritability and other psychologi

关 键 词：阿尔茨海默病症 中药 动物模型 旷场实验 转基因小鼠 

分 类 号：Q95-33[生物学—动物学]