论文部分内容阅读
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。
Statins are mainly used to lower blood LDL-C and prevent cardiovascular disease, but their clinical efficacy and tolerance to the body are still unstable. Human pro-protein convertase subtilisin 9 (PCSK9) belongs to the pro-protein invertase family and is mainly produced by the liver and secreted into the blood, which can promote the degradation of low density lipoprotein receptor (LDLR) in the liver and thus participate in the regulation of blood LDL- C level. PCSK9 population gain or loss of function mutations and blood LDL-C levels, the prevalence of cardiovascular disease are closely related. PCSK9 can be upregulated through a negative feedback mechanism to promote the degradation of LDLR, thereby reducing the efficacy of statins. Therefore, the inhibition of PCSK9 activity is expected to be a new and effective method for the treatment of hypercholesterolemia. This review summarizes the progress of PCSK9 in regulating cholesterol metabolism and its clinical application.