摘要：随着世界人口的逐渐老龄化, 老年性疾患也日见增多。本实验主要针对由脑变性引起的阿尔茨海默症（AD）进行展开，而Aβ在AD 的发病中起核心作用的假说已得到大多数人的认可。Aβ聚集可形成具有神经毒性的原纤维, 并进而形成AD的病理特征之一——老年斑。Aβ是由体内一种称为淀粉样蛋白前体蛋白（APP）经两种分泌酶加工产生，即β-分泌酶和γ-分泌酶。其中β-分泌酶的活性是APP产生Aβ的关键酶。
本实验通过高效液相色谱初步建立了一种比较直观的体外分析β-分泌酶活性的方法，建立出了酶活力动态曲线，并利用该方法为进一步分析阿尔茨海默氏症（AD）的致病机理及筛选相应的生物活性物质打下基础。在了解了β-分泌酶基本反应特性的基础上，我们以β-分泌酶抑制剂为阳性对照物验证了本分析方法的可行性。0.6um可达到34.43%的抑制程度，并随着浓度的升高，其对β-分泌酶活性所起的抑制作用越明显，呈现出了一定的线性关系。利用本评价方法，我们进一步测试了具有抗Aβ活性的姜黄素对β-分泌酶活性是否也有抑制作用，10um姜黄素即可达到17.80%的抑制效果。
关键词：β-分泌酶， 阿尔茨海默症（AD），β样淀粉蛋白（Aβ）
Abstract：As the world's population is aging, senile disease also became more and more increased. This experiment mainly caused by degenerative brain of Alzheimer's disease (AD)，and Aβ in AD playing the core function of most people who have got the hypothesis recognition. Aβ gathered can form in the neurotoxicity of the fibers, senile plaque, as one of the pathological characteristic of AD. The Aβ in vivo is called amyloid precursor protein (APP), which is by two Secrete enzymes processing produced, the beta secrete enzymes (N end), and γ-secrete enzymes (C end). Beta secretion of the enzyme’s activity is the key enzymes in APP.
This experiment is proposed by high performance liquid chromatography (HPLC), setting up a more intuitive analysis method of beta secrete enzymes. Through this analysis method, it may affect the factor of beta secretion enzyme activity for further analysis Alzheimer's disease (AD) pathogenesis mechanism and lay the foundation of corresponding screening of the biological activity material. By understanding the beta secretion basic response characteristics, we use beta secretion inhibitors for positive counterpart to this analysis, in order to verify the feasibility of the method. The beta secretion inhibitors of 0.6 um can reach 34.43% of the Inhibition degree. With the concentration increasing, the beta secretion of enzyme activity demonstrate the more obvious inhibition, presenting a certain linear relationship. Using this evaluation method, we further test the curcumin which is whether or not can resist to the activity of Aβ and have inhibition effect. The experimental results show that 10 um curcumin inhibitory effect can reach 17.80%.
Key Words: Beta secrete enzymes, Alzheimer's disease, β sample starch proteins (Aβ)
