Université de Strasbourg, EA3072, Faculté de Médecine & Faculté des Sciences du Sport, Strasbourg, France.
J Appl Physiol (1985). 2011 Nov;111(5):1477-83. doi: 10.1152/japplphysiol.00107.2011. Epub 2011 Aug 18.
Physical exercise exacerbates the cytotoxic effects of statins in skeletal muscle. Mitochondrial impairments may play an important role in the development of muscular symptoms following statin treatment. Our objective was to characterize mitochondrial function and reactive oxygen species (ROS) production in skeletal muscle after exhaustive exercise in atorvastatin-treated rats. The animals were divided into four groups: resting control (CONT; n = 8) and exercise rats (CONT+EXE; n = 8) as well as resting (ATO; n = 10) and exercise (ATO+EXE; n = 8) rats that were treated with atorvastatin (10 mg·kg(-1)·day(-1) for 2 wk). Exhaustive exercise showed that the distance that was covered by treated animals was reduced (P < 0.05). Using dihydroethidium staining, we showed that the ROS level was increased by 60% in the plantaris muscle of ATO compared with CONT rats and was highly increased in ATO+EXE (226%) compared with that in CONT+EXE rats. The maximal mitochondrial respiration (V(max)) was decreased in ATO rats compared with that in CONT rats (P < 0.01). In CONT+EXE rats, V(max) significantly increased compared with those in CONT rats (P < 0.05). V(max) was significantly lower in ATO+EXE rats (-39%) compared with that in CONT+EXE rats (P < 0.001). The distance that was covered by rats significantly correlated with V(max) (r = 0.62, P < 0.01). The glycogen content was decreased in ATO, CONT+EXE, and ATO+EXE rats compared with that in CONT rats (P < 0.05). GLUT-4 mRNA expression was higher after exhaustive exercise in CONT+EXE rats compared with the other groups (P < 0.05). Our results show that exhaustive exercise exacerbated metabolic perturbations and ROS production in skeletal muscle, which may reduce the exercise capacity and promote the muscular symptoms in sedentary atorvastatin-treated animals.
身体锻炼会加剧他汀类药物在骨骼肌中的细胞毒性作用。线粒体损伤可能在他汀类药物治疗后肌肉症状的发展中起重要作用。我们的目的是描述阿托伐他汀治疗大鼠力竭运动后骨骼肌的线粒体功能和活性氧（ROS）的产生。动物被分为四组：休息对照（CONT；n = 8）和运动大鼠（CONT+EXE；n = 8）以及休息（ATO；n = 10）和运动（ATO+EXE；n = 8）大鼠，这些大鼠接受阿托伐他汀治疗（10 mg·kg（-1）·天（-1），持续 2 周）。力竭运动表明，接受治疗的动物的运动距离减少（P < 0.05）。使用二氢乙啶染色，我们发现与 CONT 大鼠相比，ATO 大鼠的比目鱼肌 ROS 水平增加了 60%，而 ATO+EXE 大鼠的 ROS 水平增加了 226%（与 CONT+EXE 大鼠相比）。与 CONT 大鼠相比，ATO 大鼠的最大线粒体呼吸（V（max））降低（P < 0.01）。在 CONT+EXE 大鼠中，V（max）与 CONT 大鼠相比显著增加（P < 0.05）。与 CONT+EXE 大鼠相比，ATO+EXE 大鼠的 V（max）显著降低（-39%）（P < 0.001）。大鼠的运动距离与 V（max）显著相关（r = 0.62，P < 0.01）。与 CONT 大鼠相比，ATO、CONT+EXE 和 ATO+EXE 大鼠的糖原含量降低（P < 0.05）。CONT+EXE 大鼠力竭运动后 GLUT-4 mRNA 表达高于其他组（P < 0.05）。我们的结果表明，力竭运动加剧了骨骼肌的代谢紊乱和 ROS 产生，这可能会降低运动能力并促进久坐不动的阿托伐他汀治疗动物的肌肉症状。
