Päivä Hannu, Thelen Karin M, Van Coster Rudy, Smet Joél, De Paepe Boel, Mattila Kari M, Laakso Juha, Lehtimäki Terho, von Bergmann Klaus, Lütjohann Dieter, Laaksonen Reijo
Department of Internal Medicine, University Hospital of Tampere, Finland.
Clin Pharmacol Ther. 2005 Jul;78(1):60-8. doi: 10.1016/j.clpt.2005.03.006.
Myopathy, probably caused by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition in skeletal muscle, rarely occurs in patients taking statins. This study was designed to assess the effect of high-dose statin treatment on cholesterol and ubiquinone metabolism and mitochondrial function in human skeletal muscle.
Forty-eight patients with hypercholesterolemia (33 men and 15 women) were randomly assigned to receive 80 mg/d of simvastatin (n = 16), 40 mg/d of atorvastatin (n = 16), or placebo (n = 16) for 8 weeks. Plasma samples and muscle biopsy specimens were obtained at baseline and at the end of the follow-up.
The ratio of plasma lathosterol to cholesterol, a marker of endogenous cholesterol synthesis, decreased significantly by 66% in both statin groups. Muscle campesterol concentrations increased from 21.1 +/- 7.1 nmol/g to 41.2 +/- 27.0 nmol/g in the simvastatin group and from 22.6 +/- 8.6 nmol/g to 40.0 +/- 18.7 nmol/g in the atorvastatin group (P = .005, repeated-measurements ANOVA). The muscle ubiquinone concentration was reduced significantly from 39.7 +/- 13.6 nmol/g to 26.4 +/- 7.9 nmol/g (P = .031, repeated-measurements ANOVA) in the simvastatin group, but no reduction was observed in the atorvastatin or placebo group. Respiratory chain enzyme activities were assessed in 6 patients taking simvastatin with markedly reduced muscle ubiquinone and in matched subjects selected from the atorvastatin (n = 6) and placebo (n = 6) groups. Respiratory chain enzyme and citrate synthase activities were reduced in the patients taking simvastatin.
High-dose statin treatment leads to changes in the skeletal muscle sterol metabolism. Furthermore, aggressive statin treatment may affect mitochondrial volume.
肌病可能由骨骼肌中3-羟基-3-甲基戊二酰辅酶A还原酶抑制引起，服用他汀类药物的患者中很少发生。本研究旨在评估大剂量他汀类药物治疗对人体骨骼肌胆固醇和泛醌代谢以及线粒体功能的影响。
48例高胆固醇血症患者（33例男性和15例女性）被随机分配接受80mg/d辛伐他汀（n = 16）、40mg/d阿托伐他汀（n = 16）或安慰剂（n = 16）治疗8周。在基线和随访结束时采集血浆样本和肌肉活检标本。
两个他汀类药物治疗组中，作为内源性胆固醇合成标志物的血浆羊毛甾醇与胆固醇的比值均显著下降66%。辛伐他汀组肌肉菜油甾醇浓度从21.1±7.1nmol/g增加至41.2±27.0nmol/g，阿托伐他汀组从22.6±8.6nmol/g增加至40.0±18.7nmol/g（P = 0.005，重复测量方差分析）。辛伐他汀组肌肉泛醌浓度从39.7±13.6nmol/g显著降低至26.4±7.9nmol/g（P = 0.031，重复测量方差分析），但阿托伐他汀组或安慰剂组未观察到降低。对6例服用辛伐他汀且肌肉泛醌显著降低的患者以及从阿托伐他汀组（n = 6）和安慰剂组（n = 6）中选取的匹配受试者评估呼吸链酶活性。服用辛伐他汀的患者呼吸链酶和柠檬酸合酶活性降低。
大剂量他汀类药物治疗导致骨骼肌甾醇代谢发生变化。此外，积极的他汀类药物治疗可能影响线粒体体积。
