中药Ⅰ号方对APP/PS1双转基因模型小鼠APP代谢的影响  

Effect of a Chinese traditional prescription PN-1 on the amyloid precursor protein processing in transgenic mouse model of Alzheimer's disease

作　　者：隋小龙[1] 梁良[1] 张玲[1] 朱华[1] 徐艳峰[1] 黄澜[1] 徐玉环[1] 韩云林[1] 姚志刚[1] 秦川[1] 邓巍[1] 

机构地区：[1]中国医学科学院,北京协和医学院,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》2014年第6期49-53,I0004,I0005,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家863课题(编号:SS2012AA022613)

摘　　要：目的研究中药I号方对APP/PS1双转基因模型小鼠APP代谢的影响。方法将5月龄APP/PS1双转基因模型小鼠随机分为模型组(vehicle)、中药Ⅰ号方低剂量组(0.6 g/kg)、中剂量组(1.2 g/kg)和高剂量组(2.4 g/kg),并以同窝阴性小鼠作为正常对照组(wild-type,WT),每组16只,雌雄各半。给药小鼠每天灌胃一次,模型组和正常对照组分别给予等体积的双蒸水灌胃。给药四个月后,用免疫组化和Western blot检测淀粉样前体蛋白(APP)及其代谢产物和分解酶的变化。结果 Western blot结果显示,与模型组相比,治疗组低剂量、中剂量和高剂量给药组能显著降低APP分解酶(ADAM10和BACE1)(P<0.01)及APP的分解产物的量,如:β-CTF(C99)、α-CTF(C83)、s APPα、s APPβ(P<0.01)。结论中药I号方通过影响APP的分解过程减少淀粉样蛋白(β-amyloid peptide,Aβ)的生成,减少脑内老年斑的沉积。Objective To investigate the effects of a Chinese traditional prescription PN-1 on the amyloid precursor protein （ APP） processing in a transgenic mouse model of Alzheimer’ s disease.Methods Eighty 5-month old transgenic mice were randomly divided into vehicle group, PN-1 low （0.6 g/kg）, medium （1.2 g/kg） and high （2.4 g/kg） dose groups.Both the wild-type littermates and model group with distilled water administration were chosen as control groups.Sixteen mice （8 males and 8 females） in each group were given intragastrically PN-1 or distilled water once a day for 4 months.After the drug administration, immunohistochemistry, ELISA and Western blot were performed to measure the products of amyloid precursor protein （APP） and the associated enzymes （ADAM10 and BACE1）.Results Compared with the control group, β-CTF （C99）, α-CTF （C83）, sAPPα, sAPPβ, ADAM10 and BACE1 were significantly decreased in the low, medium and high dose groups （ P〈0.01 ） .Conclusions PN-1 alleviates cognitive deficits in an Alzheimer’ s disease transgenic mouse model through influencing the processing of APP.

关 键 词：中药Ⅰ号方 阿尔茨海默病 APP分解酶 APP/PS1双转基因AD模型小鼠 

分 类 号：Q95-33[生物学—动物学]