前蛋白转化酶枯草溶菌素9抑制剂:调节血脂的新策略

Proprotein convertase subtilism/kexin type 9 inhibitors:a new strategy of regulating cholesterol

前蛋白转化酶枯草溶菌素9(PCSK9)主要促进肝脏中低密度脂蛋白受体(LDLR)降解来调节胆固醇代谢。PCSK9功能获得型基因突变是导致常染色体显性遗传性高胆固醇血症的原因之一,而PCSK9功能缺失型基因突变则与低水平的低密度脂蛋白胆固醇(LDL-C)和冠心病发生的减少有关。目前,PCSK9已经成为新的调节血脂药物作用靶点,两种单克隆抗体类PCSK9抑制剂已完成Ⅱ、Ⅲ期临床试验。本文就单克隆抗体类PCSK9抑制剂的最新研究进展作一综述。

The proprotein convertase subtilisin/kexin type 9 （PCSK9） regulates cholesterol metabolism mainly by targeting the low-density lipoprotein receptor （LDLR） for degradation in the liver. Gain-of-function mutations in PCSK9 is one of the genetic causes of autosomal dominant hypercholesterolaemia. Conversely, loss- of- function mutations are associated with lower concentrations of LDL cholesterol （LDL- C） and reduced coronary heart disease. Now, PCSK9 has emerged as a new drug target for the treatment of hypercholesterolemia. Two PCSK9 inhibitors of monoclonal antibody have completed phase Ⅱ and phase Ⅲ clinical trials. This paper is a comprehensive review of the latest research advances in PCSK9 inhibitors of monoclonal antibody.