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红曲米和辅酶Q10作为安全的替代品,用于克服高脂血症大鼠中阿托伐他汀引起的肌病。

Red yeast rice and coenzyme Q10 as safe alternatives to surmount atorvastatin-induced myopathy in hyperlipidemic rats.

作者信息

Abdelbaset Marwan, Safar Marwa M, Mahmoud Sawsan S, Negm Seham A, Agha Azza M

机构信息

a Department of Pharmacology, Medical Research Division, National Research Centre, El Tahrir Street, 12622 Giza, Egypt.

出版信息

Can J Physiol Pharmacol. 2014 Jun;92(6):481-9. doi: 10.1139/cjpp-2013-0430. Epub 2014 Apr 28.

DOI:10.1139/cjpp-2013-0430
PMID:24896301
Abstract

Statins are the first line treatment for the management of hyperlipidemia. However, the primary adverse effect limiting their use is myopathy. This study examines the efficacy and safety of red yeast rice (RYR), a source of natural statins, as compared with atorvastatin, which is the most widely used synthetic statin. Statin interference with the endogenous synthesis of coenzyme Q10 (CoQ10) prompted the hypothesis that its deficiency may be implicated in the pathogenesis of statin-associated myopathy. Hence, the effects of combination of CoQ10 with either statin have been evaluated. Rats were rendered hyperlipidemic through feeding them a high-fat diet for 90 days, during the last 30 days of the diet they were treated daily with either atorvastatin, RYR, CoQ10, or combined regimens. Lipid profile, liver function tests, and creatine kinase were monitored after 15 and 30 days of drug treatments. Heart contents of CoQ9 and CoQ10 were assessed and histopathological examination of the liver and aortic wall was performed. RYR and CoQ10 had the advantage over atorvastatin in that they lower cholesterol without elevating creatine kinase, a hallmark of myopathy. RYR maintained normal levels of heart ubiquinones, which are essential components for energy production in muscles. In conclusion, RYR and CoQ10 may offer alternatives to overcome atorvastatin-associated myopathy.

摘要

他汀类药物是治疗高脂血症的一线用药。然而,限制其使用的主要不良反应是肌病。本研究比较了天然他汀来源的红曲米(RYR)与使用最广泛的合成他汀阿托伐他汀的疗效和安全性。他汀类药物干扰辅酶Q10(CoQ10)的内源性合成,由此提出假说,即CoQ10缺乏可能与他汀相关肌病的发病机制有关。因此,已对CoQ10与任一他汀联合使用的效果进行了评估。通过给大鼠喂食高脂饮食90天使其血脂升高,在饮食的最后30天,每天用阿托伐他汀、RYR、CoQ10或联合用药方案对其进行治疗。在药物治疗15天和30天后监测血脂谱、肝功能检查和肌酸激酶。评估心脏中CoQ9和CoQ10的含量,并对肝脏和主动脉壁进行组织病理学检查。RYR和CoQ10相对于阿托伐他汀具有优势,即它们能降低胆固醇而不升高肌酸激酶,而肌酸激酶升高是肌病的一个标志。RYR维持心脏泛醌的正常水平,而泛醌是肌肉能量产生的必需成分。总之,RYR和CoQ10可能为克服阿托伐他汀相关肌病提供替代方案。

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