%0 Journal Article
%T PCSK9抑制剂的心血管保护机制研究进展<br>Research Progress of Cardiovascular Protection Mechanism of PCSK9 Inhibitors
%A 李慧
%A 李飞
%J Advances in Clinical Medicine
%P 2192-2198
%@ 2161-8720
%D 2025
%I Hans Publishing
%R 10.12677/acm.2025.153854
%X PCSK9抑制剂通过靶向调控低密度脂蛋白受体(LDLR)降解&#65292;已成为动脉粥样硬化性心血管疾病(ASCVD)治疗的革命性策略。本文结合国内外研究进展&#65292;从以下三方面进行系统阐述&#65306;1) 分子机制&#65306;PCSK9通过催化结构域与LDLR结合&#65292;介导其溶酶体降解&#65292;而抑制剂可恢复LDLR再循环&#65292;降低LDL-C达60%~70%&#65307;2) 药物研发&#65306;单克隆抗体(Alirocumab、Evolocumab)显著降低MACE风险15%~20%&#65292;RNA干扰疗法(Inclisiran)实现半年一次给药&#65292;口服小分子(MK-0616)突破生物制剂限制&#65307;3) 多途径保护&#65306;除降脂外&#65292;PCSK9抑制剂通过抑制炎症(hs-CRP降低37%)、调节免疫(Treg/Th17平衡)及改善内皮功能(FMD提升12%)发挥协同效应。未来需聚焦长期安全性验证、成本效益优化及联合疗法开发&#65292;以全面提升ASCVD的防治水平。<br>PCSK9 inhibitors have become a revolutionary strategy for the treatment of atherosclerotic cardiovascular disease (ASCVD) by targeting and regulating low-density lipoprotein receptor (LDLR) degradation. Based on the research progress at home and abroad, this paper systematically describes the following three aspects: 1) Molecular mechanism: PCSK9 binds to LDLR through catalytic domain, mediates lysosomal degradation, while inhibitors can restore LDLR recycling and reduce LDL-C by 60%~70%; 2) Drug development: Monoclonal antibodies (Alirocumab, Evolocumab) significantly reduced the risk of MACE by 15%~20%, RNA interference therapy (Inclisiran) achieved semi-annual administration, and oral small molecules (MK0616) broke the limit of biologics; 3) Multipathway protection: In addition to lipid-lowering, PCSK9 inhibitors play a synergistic role by inhibiting inflammation (37% reduction in hs-CRP), modulating immunity (Treg/Th17 balance), and improving endothelial function (12% increase in FMD). The future needs to focus on long-term safety validation, cost-effectiveness optimization, and combination therapy development to comprehensively improve the level of ASCVD prevention and treatment.
%K PCSK9抑制剂&#65292
%K 低密度脂蛋白受体(LDLR)&#65292
%K 动脉粥样硬化性心血管疾病(ASCVD)&#65292
%K RNA干扰疗法&#65292
%K 抗炎机制&#65292
%K 脂蛋白(a) [Lp(a)]<br>PCSK9 Inhibitor
%K Low-Density Lipoprotein Receptor (LDLR)
%K Atherosclerotic Cardiovascular Disease (ASCVD)
%K RNA Interference Therapy
%K Anti-Inflammatory Mechanism
%K Protein (a) [Lp(a)]
%U http://www.hanspub.org/journal/PaperInformation.aspx?PaperID=110061