中药Ⅰ号方对 APP／PS1双转基因模型小鼠 APP 代谢的影响

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）、sAPPα、sAPPβ（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 precur-sor protein ( APP) processing in a transgenic mouse model of Alzheimer’ s disease.Methods Eighty 5-month old trans-genic 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 Com-pared 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.