他汀类药物在临床应用中的不良反应及产生机制

The adverse effects and mechanism of statins in clinical application

他汀类药物作为胆固醇合成早期阶段的竞争性抑制剂,抑制3-羟基-3-甲基戊二酰辅酶A(3-hydroxy-3-methyl glutaryl coenzyme A reductase,HMG-CoA)还原酶的活性,使HMG-CoA向甲羟戊酸的转化途径受阻,阻碍肝脏合成内源性胆固醇,代偿性地增加肝细胞膜上低密度脂蛋白受体,从而降低血浆中低密度脂蛋白(LDL)水平,达到治疗和预防心脑血管疾病的目的。本文对他汀类药物使用过程中副作用的细胞代谢途径、产生机制以及临床表现进行了综述,探讨了他汀类药物调脂过程中,在肌肉、肝脏等方面引起的副作用表现及其分子机制。

As a competitive inhibitor in the synthesis of cholesterol during the early stage,statins inhibit the activity of 3-hydroxy-3-methylcoenzyme A（ HMG-Co A） reductase. In this way,statins block the conversion from HMG-Co A to mevalonate and hinder the synthesis of endogenous cholesterol in hepar. Through all these methods above,statins increase low-density lipoprotein（ LDL） receptor on hepatocyte membrane by a compensatory mechanism,which contributes to the decrease of LDL in the plasma. Consequently,statins play an important role in the treatment and prevention of cardiovascular diseases. Here,we aim to summarize the metabolic pathways,the mechanism of action and clinical manifestations of statinsinduced side effects. What is more,the performance and molecular mechanism of these side effects,especially on hepar and muscle during the process of lipid balance are discussed in this review.