The strategy to avoid drug-induced skeletal muscle injury involved in monocarboxylate transporter

虽然运动和药物治疗对预防动脉炎疾病的进展很重要，但运动表现会增加药物引起的肌肉损伤。因此，需要阐明这一机制，以避免肌肉疾病。由于运动表现诱导单羧酸转运体（MCT）4的表达，我们专注于MCT 4和HMG-CoA还原酶抑制剂（如他汀类药物诱导的肌肉损伤）之间的关联。他汀类药物阿托伐他汀（Atorvastatin）可显著降低体外培养的RD细胞的存活细胞数，引起细胞形态学改变和caspase-3/7激活，并诱导骨骼肌模型细胞中MCT 4的表达。两种针对MCT 4的siRNA（10 nM）在转染到RD细胞后72 h显著降低了MCT 4的表达。阿托伐他汀诱导的RD细胞损伤被转染到RD细胞的MCT 4 siRNA阻断。这些结果表明，他汀类药物诱导的肌肉损伤的机制与MCT 4的表达。

Although exercise and drug therapy is important to prevent progress of an arteriosclerotic disease, exercise performance leads to increase drug-induced muscle injury. So the elucidation of this mechanism is needed for avoiding muscular disorder. Since exercise performance induced the expression of monocarboxylate transporter (MCT) 4, we focused on the association between MCT4 and HMG-CoA reductase inhibitors such as statins-induced muscle injury. Atorvastatin, one of statins reduced the number of viable cells and caused dramatic morphological changes and caspase-3/7 activation, and induced MCT4 expression levels in RD cell line as a model of in vitro skeletal muscle. Two siRNAs (10 nM) for MCT4 significantly decreased MCT4 expression at 72 h after transfected to RD cells. Atorvastatin-induced RD cell injury was blocked by MCT4 siRNAs transfected to RD cells. These results suggest that the mechanism of statin-induced muscle injury was associated with MCT4 expression.