摘要
背景：已采用多种方法对进行性脑部疾病阿尔茨海默氏病进行治疗性内插。因此，β-分泌酶的抑制对于预防疾病的早期发展很重要。目的：本研究旨在从太平洋无须鳕酶水解物中纯化和鉴定新型β-分泌酶抑制肽。 方法：采用Sephadex G-25柱色谱和十八烷基硅烷（ODS）C18反相HPLC进行连续纯化，分离出有效的β-分泌酶抑制肽。使用分离的肽序列合成了总共七个肽。稳定转染了人类“瑞典”淀粉样蛋白前体蛋白（APP）突变APP695（SH-SY5YAPP695swe）的SH-SY5Y细胞用作体外模型系统，研究了Leu-Asn肽对APP加工的影响。 结果：来自鱼蛋白水解产物的纯化肽（Ser-Leu-Ala-Phe-Val-Asp-Asp-Val-Leu-Asn）的β-分泌酶抑制活性（IC50）为18.65μM，二肽Leu-Asn为最有效的β-分泌酶抑制剂（IC50值= 8.82μM）。当比较所有七个肽时，通过Lineweaver-Burk图和Dixon图（Ki值= 4.24μM）发现Leu-Asn二肽的抑制模式具有竞争性。在SH-SY5Y细胞中用Leu-Asn肽处理24小时导致β-淀粉样蛋白（Aβ）的产生呈剂量依赖性减少。 结论：因此，这项研究结果表明，海洋生物来源的β-分泌酶抑制肽可能成为开发抗痴呆剂的保健品或药物的潜在候选者。
关键词: β-分泌酶抑制活性，鱼蛋白水解物，肽，β-淀粉样蛋白，淀粉样前体蛋白，阿尔茨海默氏病。
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