酸性肽对血管性痴呆小鼠学习记忆力和脑组织APP、BACE和tau蛋白表达的影响

Influence of acidic peptide on learning and memory abilities and levels of APP,BACE and tau protein in brains of vascular dementia mice

目的:观察酸性肽对血管性痴呆(VD)小鼠学习记忆力及脑内淀粉样前体蛋白(APP)、β-分泌酶(BACE)及tau蛋白表达的影响。方法:60只健康昆明种小鼠,随机分成6组,每组10只。除对照组外,其余5组小鼠给予高脂食物灌胃、颈动脉局部缺血及再灌注手术,建立VD小鼠模型,随后分别灌胃生理盐水(模型组)、0.3g/kg脑复康(脑复康组)和20、40和80mg/(kg·d)的酸性肽(低、中及高剂量酸性肽组),1次/d,共15d。用跳台试验检测小鼠的学习和记忆能力,免疫组化法测定脑组织APP、BACE及tau蛋白的表达。结果:6组小鼠学习能力跳台实验错误次数及受电击时间、记忆能力跳台实验错误次数及受电击时间及脑组织APP、BACE及tau蛋白表达差异均有统计学意义(F分别为6.544、2.991、11.179、6.100、484.218、59.317和40.448,P均<0.01)。与模型组相比,低、中剂量酸性肽组小鼠学习及记忆能力提高(P<0.05)。3个酸性肽组APP及BACE表达水平降低(P<0.05),低、中剂量酸性肽组与对照组比较,tau蛋白表达水平差异无统计学意义(P>0.05)。结论:适宜剂量的酸性肽可通过降低VD小鼠脑内APP和BACE的水平,改善其学习记忆力。

Aim：To study the influence of acidic peptide（AP） on amyloid precursor protein（APP）,B-site APP cleaving enzyme（BACE） and tau protein in the brains of mice with vascular dementia（VD）.Methods：A total of 60 healthy mice were randomly divided into 6 groups,and 10 in each group.Except 10 mice in A group,the mice in other 5 groups（B,C,D,E and F groups） were to make VD model and then poured physiological saline,0.3 g/kg of Naofukang,20,40 and 80 mg/kg AP,respectively for 15 days,and one time/day.The learning and memory abilities of the mice were detected by step-down avoidance test,and the expressions of APP,BACE and tau protein in brain tissue by immunohistochemistry staining.Results：The differences in error numbers and electric shock times in step-down avoidance test for learning and memory abilities detection,and the expressions of APP,BACE and tau protein in brain tissues among the 6 groups were significant（F was 6.544,2.991,11.179,6.100,484.218,59.317and 40.448,P0.01）.20 and 40 mg/（kg·d） AP could improve the learning and memory abilities of VD mice（P0.05）.Conclusion：AP can reduce the levels of APP and BACE in the brains of VD mice,and improve their learning and memory abilites.