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他汀类药物相关性肌病

Authors
Robert S Rosenson, MD
Steven K Baker, MSc, MD
Section Editor
Mason W Freeman, MD
Deputy Editor
David M Rind, MD
Translators
陈俊伟, 副教授

引言

他汀类药物是降低血清胆固醇浓度的主要药物类别，用于进行冠状动脉疾病一级和二级预防。(参见“一级预防中的调脂(包括高胆固醇血症)治疗”和“二级预防中的调脂(包括高胆固醇血症)治疗”和“心血管疾病二级预防中降脂治疗的强度”)

他汀类药物既有效且一般较安全。虽然他汀类药物的肌肉毒性仍然是一个顾虑，但严重的肌病罕见，仅累及约0.1%的患者[1,2]。本文将讨论他汀类药物相关的肌肉综合征，包括肌痛和肌肉损伤。他汀类药物的其他副作用将单独讨论。(参见“他汀类药物的作用、副作用与给药说明”)

发病机制

他汀类药物引起肌肉毒性的机制尚不十分清楚。它们可抑制羟甲戊二酰辅酶A(hydroxy-methyl-glutaryl-coenzyme A, HMG-CoA)转化为甲羟戊酸，这种转化是胆固醇合成的一个重要早期步骤。

各种他汀类药物可能对辅酶Q10(coenzyme Q10, CoQ10，泛醌)的合成具有不同的影响，CoQ10在肌细胞能量生产中扮演着重要角色。据推测，骨骼肌中泛醌的减少可能促发他汀类药物诱导的肌肉损伤。一些研究发现，他汀类药物可降低骨骼肌和血浆泛醌浓度[3-5]；然而，其他研究并无这一发现[6]，并且不同的研究对于他汀类药物治疗是否可降低骨骼肌中泛醌的水平得出了不一致的结论[5,7,8]。长期使用辛伐他汀治疗(10-40mg/d，持续时间>12个月)可减少骨骼肌中泛醌含量，并降低了最大线粒体氧化磷酸化的能力[9]。

一项研究发现，采用高剂量他汀类药物治疗的患者，骨骼肌的植物甾醇水平增高[5]。尤其是谷甾醇增加了约50%。该研究的作者提出，这些植物甾醇细胞水平的增加可促发他汀类药物的肌肉毒性。β谷甾醇是一种AMP活化蛋白激酶的激活物，这种酶可抑制乙酰CoA辅羧酶。这会导致脂肪合成减少及β-氧化增加。初步证据表明，不能耐受他汀类药物的患者使用洛伐他汀会出现脂肪酸氧化(fatty acid oxidation, FAO)增加，提示一种内源性FAO异常[10]。他汀类药物增加线粒体肉碱酰基肉碱转位酶的表达，这种作用可能促发FAO变化[11]。

                              

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Literature review current through: 2017-06 . | This topic last updated: 2016-03-11.
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