PCSK9抑制剂在脂代谢中的研究进展

Progress in the study of PCSK9 inhibitors in lipid metabolism

关键词:  PCSK9  PCSK9抑制剂  LDL-C  ASCVD

Key words:  PCSK9  PCSK9 inhibitors  low-density lipoprotein-cholesterol  ASCVD

摘要:

前蛋白转换酶枯草溶菌素9（PCSK9）是参与调节低密度脂蛋白受体（LDLR）表达，通过促进溶酶体对LDLR的消化作用降低了细胞表面LDLR的密度，进而导致血浆低密度脂蛋白胆固醇（LDL-C）升高。仅在开始研究10年间，PCSK9抑制剂就被全球多个药监局获批上市，2015年美国FDA批准evolocumab和alirocumab用于临床。目前研发的干预PCSK9的方式包括：单克隆抗体、小干扰（siRNA）、反义寡核苷酸、疫苗接种等。但PCSK9抑制剂的临床使用尚未普及。

Abstract:

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease involved in the regulation of LDL receptor (LDLR) expression and apolipoprotein B（apoB） lipoprotein cholesterol metabolism, which can prevent LDLR from escaping lysosome digestion, thereby reduce cell surface LDLR density and lead to the increase of plasma low density lipoprotein cholesterol (LDL-C). PCSK9 inhibitors have been approved by many drug regulatory agencies worldwide within only 10 years of research. In 2015, the FDA approved evolocumab and alirocumab were produced for clinical use. At present, approaches of PCSK9 intervention include monoclonal antibody, small interference (siRNA), antisense oligonucleotides, vaccination et al. Nevertheless, the clinical use of PCSK9 inhibitors has not been popularized.