肝细胞前蛋白转化酶枯草杆菌蛋白酶9降脂药物调控研究进展  

Research progress on the regulation of hepatocyte proprotein convertase subtilisin/kexin type 9 lipid-lowering drugs

作　　者：刘素素 俞德帅 杨双杰 乔艳芳 柴欣楼 LIU Susu;YU Deshuai;YANG Shuangjie;QIAO Yanfang;CHAI Xinlou(School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学中医学院,北京100029

出　　处：《中华中医药杂志》2023年第11期5381-5384,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家科技重大专项基于大数据的中药新药研发(No.2019ZX09201004-001-021)。

摘　　要：高脂血症可引起动脉粥样硬化、脑卒中、冠心病等疾病,高脂血症患者患心血管疾病的风险大约是总胆固醇水平正常的人的两倍。肝低密度脂蛋白受体(LDLR)与血液中低密度脂蛋白结合,通过内吞作用调节胆固醇的稳态,而前蛋白转化酶枯草杆菌蛋白酶9(PCSK9)可竞争性的结合LDLR,介导LDLR的降解,导致高脂血症。PCSK9抑制剂的临床试验已经证明可减少心血管事件的发生,但是其存在高昂价格及不良反应。文章综述了PCSK9合成的转录因子及下游分子的最新进展,并着重介绍了靶向LDLR-PCSK9通路的相关药物及作用机制,旨在对PCSK9-LDLR通路的研究提供参考以及为开发降脂中药开辟新的路径。Hyperlipidemia can cause atherosclerosis,stroke,coronary heart disease,and other diseases,and the risk of cardiovascular disease in patients with hyperlipidemia is approximately twice as high as that in people with normal total cholesterol levels.The hepatic low-density lipoprotein receptor(LDLR)binds to blood low-density lipoprotein and regulates cholesterol homeostasis through endocytosis,whereas proprotein convertase subtilisin/kexin type 9(PCSK9)competitively binds to the LDLR and mediates the degradation of the LDLR,leading to hyperlipidemia.Clinical trials of PCSK9 inhibitors have demonstrated that they can reduce cardiovascular events;however,they are associated with a high price tag and adverse effects.This article reviews the recent progress of transcription factors and downstream molecules of PCSK9 synthesis,and highlights relevant drugs targeting the LDLR-PCSK9 pathway and their mechanisms of action,aiming to provide a reference for the study of the PCSK9-LDLR pathway as well as open up new pathways for the development of lipid-lowering traditional Chinese medicines.

关 键 词：高脂血症 前蛋白转化酶枯草杆菌蛋白酶9(PCSK9) 低密度脂蛋白受体 新药研发 中药降脂 

分 类 号：R285[医药卫生—中药学]