| 摘要: |
| 他汀类药物主要用于降低血低密度脂蛋白胆固醇（LDL-C）以及预防心血管疾病，但其临床疗效和机体的耐受性尚存在不稳定性。人类前蛋白转化酶枯草溶菌素9（PCSK9）属于前蛋白转化酶家族，主要由肝脏产生并分泌入血，可促进肝脏中低密度脂蛋白受体（LDLR）的降解，从而参与调控血LDL-C水平。人群中PCSK9的功能获得型或缺失型基因突变与血LDL-C含量、心血管疾病患病率密切相关。可通过负反馈机制上调PCSK9，促进LDLR的降解，从而降低他汀类药物的疗效。因此，抑制PCSK9活性可望成为治疗高胆固醇血症的一种新的有效方法。本文主要综述PCSK9调节胆固醇代谢及其临床应用的研究进展。 |
| 关键词: 胆固醇代谢 低密度脂蛋白胆固醇 低密度脂蛋白受体 前蛋白转化酶枯草溶菌素9 |
| DOI：10.16781/j.0258-879x.2017.11.1425 |
| 投稿时间：2017-04-25修订日期：2017-06-24 |
| 基金项目:国家重点基础研究发展计划（"973计划"，2013CB530603），国家自然科学基金（31730042）. |
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| Proprotein convertase subtilisin/kexin type 9 as a new target of anticholesteremic agent:an update |
| LI Hao,TAO Long-xiao,ZHANG Wei-ping* |
(Department of Pathophysiology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China
*Corresponding author) |
| Abstract: |
| Statins are mainly used to reduce the content of low-density lipoprotein-cholesterol (LDL-C) and to prevent cardiovascular disease, but its clinical efficacy and the tolerance of body are still uncertain. Human proprotein convertase subtilisin/kexin type 9 (PCSK9), a member of pre-protein convertase family, is mainly produced in the liver and then released into blood, and plays an important role in regulating plasma LDL-C levels by promoting the degradation of low-density lipoprotein receptor (LDLR) in the liver. Both gain-of-function-and loss-of-function-mutation of PCSK9 have great impact on circulating LDL-C levels and the risk of cardiovascular diseases. Statins can up-regulate the expression of PCSK9 through negative feedback regulation by decreasing hepatic cholesterol. As a result, PCSK9 can reduce the efficiency of statins by promoting the degradation of LDLR; therefore inhibiting PCSK9 is expected to be an effective treatment for hypercholesterolemia. In this paper we reviewed the function of PCSK9 in cholesterol metabolism and its clinical application. |
| Key words: cholesterol metabolism low-density lipoprotein-cholesterol low-density lipoprotein receptors proprotein convertase subtilisin/kexin type 9 |
