PCSK9单克隆抗体：12年，从基础研究到临床应用
PCSK9 Monoclonal Antibody: 12 Years, from Basic Research to Clinical Application
DOI: 10.12677/ACM.2019.911194, PDF,    科研立项经费支持
作者: 应航鹰, 王嘉程, 周斌全*：浙江大学附属邵逸夫医院心内科，浙江省心血管介入与再生修复研究重点实验室，浙江 杭州
关键词: PCSK9抑制剂；阿利西尤单抗；依洛尤单抗；PCSK9 Inhibitor； Alirocumab； Evolocumab
摘要: PCSK9是一种属于枯草杆菌蛋白酶亚族，由肝脏合成并负责调控蛋白质活性的丝氨酸蛋白酶。有研究发现，鼠科动物实验中PCSK9过表达能引起LDL-R (低密度脂蛋白受体)减少，LDL-C (低密度脂蛋白胆固醇)升高，同时人群中PCSK9功能缺失突变降低LDL-C水平。而血脂异常和动脉粥样硬化是缺血性的心血管疾病的主要危险因素。因此，PCSK9抑制剂迅速成为血脂管理的新热点。目前，临床应用较多的单抗主要有Alirocumab (阿利西尤单抗)、Evolocumab (依洛尤单抗)和Bococizumab。虽然PCSK9在临床血脂控制上有很大的潜力，但仍存在影响认知功能及血糖波动无法忽视的等副作用。本文完整地归纳总结了PCSK9的作用机制、临床转化、临床副作用及临床展望。
Abstract: PCSK9, subfamily of Proprotein convertase subtilisin, is a serine protease synthesized by the liver and responsible for regulating the activity of proteins. A recent study on murine founded that overexpression of PCSK9 led to the decrease in LDL-R (low-density lipoprotein receptor) and an increase in LDL-C (low-density lipoprotein cholesterol). Another experiment in human suggested that deficiency PCSK9 reduced LDL-C level. Since dyslipidemia and atherosclerosis are major risk factors for ischemic cardiovascular diseases, PCSK9 inhibitors rapidly become a new hotspot of blood lipid management. Antibodies applied clinically are Alirocumab, Evolocumab and Bococizumab. Despite the great potential in clinical lipid control, there are still side effects (e.g. cognitive function impairment and plasma glucose fluctuation) that cannot be ignored. In this review, the mechanism, clinical transformation, side effects and clinical prospect of PCSK9 were summarized.
文章引用：应航鹰, 王嘉程, 周斌全. PCSK9单克隆抗体：12年，从基础研究到临床应用[J]. 临床医学进展, 2019, 9(11): 1255-1260. https://doi.org/10.12677/ACM.2019.911194

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