Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
Muscle Nerve. 2011 Sep;44(3):393-401. doi: 10.1002/mus.22081.
Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, are widely used drugs for hyperlipidemia and are generally well-tolerated, but the can produce skeletal muscle toxicity. The molecular mechanisms driving statin myopathy are unknown. We investigated the effects of statin treatment and eccentric (damaging) exercise on transcriptional patterns between statin myopathy (Sym; N = 9) and statin-tolerant subjects (Asym; N = 6).
Skeletal muscle biopsies were collected 6 h post-exercise at baseline and after statin treatment. Subjects performed concentric (non-damaging) exercise with one leg and concentric + eccentric exercise with the other leg using a cross-over design between time-points.
Sym as compared with Asym demonstrated decreased skeletal muscle gene expression for oxidative phosphorylation-related and mitochondrial ribosomal protein genes before and after statin treatment with eccentric exercise.
These results suggest that pre-existing deficiencies in energy production may contribute to the development of symptoms during statin therapy, especially when muscle is exposed to eccentric exercise.
羟甲基戊二酰辅酶 A（HMG-CoA）还原酶抑制剂，即他汀类药物，被广泛用于治疗高脂血症，且通常具有良好的耐受性，但可能会产生肌肉毒性。导致他汀类药物性肌病的分子机制尚不清楚。我们研究了他汀类药物治疗和离心（损伤）运动对他汀类药物性肌病（Sym；N = 9）和他汀类药物耐受者（Asym；N = 6）之间转录模式的影响。
在基线和他汀类药物治疗后，在运动后 6 小时采集骨骼肌活检。使用交叉设计，在一个腿上进行向心（非损伤）运动，在另一个腿上进行向心+离心运动。
与 Asym 相比，Sym 在他汀类药物治疗前后的离心运动中，与氧化磷酸化相关的骨骼肌基因表达和线粒体核糖体蛋白基因表达降低。
这些结果表明，在他汀类药物治疗期间，能量产生的预先存在的缺陷可能会导致症状的发展，尤其是当肌肉暴露于离心运动时。
