Pcsk9抑制剂的药理学和治疗潜力

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引用次数: 0

摘要

蛋白转化酶枯草素/可辛9型(PCSK9)是一种通过破坏LDL受体间接调节血清LDL胆固醇的蛋白水解酶。在临床研究中阐明了蛋白转化酶subtilisin/Kexin type9 (PCSK9)抑制剂在胆固醇调节中的主要作用。它在肝脏中产生,但也存在于肾脏和肠道中。它能阻止HMGCo合成胆固醇。SREBP-2是一种由他汀类药物诱导的还原酶。以剂量依赖的方式,增加SREBP-2水平可增强LDL-R和PCSK9基因表达。至少,已经开发了两种方法来克服PCSK9禁止的血浆水平。这是LDLR试验,多克隆抗体和感知寡核苷酸。低剂量的他汀类药物治疗与蛋白转化酶枯草杆菌素/Kexin 9型抑制剂将最有效地降低LDL和避免他汀类药物的不良反应。在多项长期试验中,他汀类药物已被发现可将心血管疾病死亡率降低30%,卒中发病率降低20%。通过这种方式,我们得出PCSK9在高胆固醇血症中的作用。
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Pharmacology and Therapeutic Potential of Pcsk9 Inhibitors
Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a proteolytic enzyme that indirectly regulates serum LDL cholesterol by destroying LDL receptors. The main role of proprotein convertase subtilisin/Kexin type9 (PCSK9) inhibitor in cholesterol regulation was elucidated in clinical studies. It is produced in the liver but is also present in the kidney and intestine. It prevents HMGCo from synthesizing cholesterol. SREBP-2 is a reductase that is induced by statins. In a dose-dependent manner, increasing SREBP-2 levels enhanced LDL-R and PCSK9 gene expression. At the minimum, two procedures have been developed to overcome the plasma level of PCSK9 prohibit. This is the LDLR test, polyclonal antibodies, and sentience oligonucleotide. Lower dosage statin treatment with a proprotein convertase subtilisin/Kexin type9 inhibitor will be most efficient in lowering LDL and avoiding statin adverse effects. In multiple long-term trials, statins have been found to reduce cardiovascular mortality by 30% and stroke incidence by 20%. In this way, we conclude the role of PCSK9 in hypercholesterolemia.
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