• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochimica et Biophysica Acta. General Subjects >Structural and functional characterization of simvastatin-induced myotoxicity in different skeletal muscles
【24h】

Structural and functional characterization of simvastatin-induced myotoxicity in different skeletal muscles

机译：辛伐他汀诱导的不同骨骼肌肌毒性的结构和功能表征

获取原文
获取原文并翻译 | 示例
       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background Statins are the most commonly used drugs for the treatment of hypercholesterolemia. Their most frequent side effect is myotoxicity. To date, it remains unclear whether statins preferentially induce myotoxicity in fast- or in slow-twitch muscles. Therefore, we investigated these effects on fast- (extensor digitorum longus; EDL), slow- (soleus; SOL), and mixed-twitch muscles (diaphragm; DIA) in rats by comparing their contractile and molecular structural properties. Methods Simvastatin-induced functional changes were determined by muscle contraction measurements, and drug-induced molecular changes were investigated using Fourier transform infrared (FTIR) and attenuated total reflectance (ATR) FTIR spectroscopy. Results With simvastatin administration (30 days, 50 mg/kg), a depression in the force-frequency curves in all muscles was observed, indicating the impairment of muscle contractility; however, the EDL and DIA muscles were affected more severely than the SOL muscle. Spectroscopic findings also showed a decrease in protein, glycogen, nucleic acid, lipid content and an increase in lipid order and lipid dynamics in the simvastatin-treated muscles. The lipid order and dynamics directly affect membrane thickness. Therefore, the kinetics and functions of membrane ion channels were also affected, contributing to the statin-induced impairment of muscle contractility. Furthermore, a reduction in α-helix and β-sheet and an increase in random coil, aggregated and antiparallel β-sheet were observed, indicating the protein denaturation. Spectral studies showed that the extent of molecular structural alterations in the muscles following simvastatin administration was in the order EDL > DIA > SOL. Conclusions Simvastatin-induced structural and functional alterations are more profound in the fast-twitch than in the slow-twitch muscles. General significance Myotoxic effects of simvastatin are primarily observed in the fast-twitch muscles.
机译：背景他汀类药物是用于治疗高胆固醇血症的最常用药物。它们最常见的副作用是肌毒性。迄今为止，尚不清楚他汀类药物是否会优先诱导快肌或慢肌的肌毒性。因此，我们通过比较大鼠的收缩和分子结构特性，研究了它们对快（伸指长肌; EDL），慢（比目鱼肌; SOL）和混合肌（横隔膜; DIA）的影响。方法通过肌肉收缩测定法确定辛伐他汀引起的功能变化，并使用傅立叶变换红外光谱（FTIR）和衰减全反射率（ATR）FTIR光谱研究药物诱导的分子变化。结果辛伐他汀给药（30天，50 mg / kg）后，所有肌肉的力频曲线均出现下降，表明肌肉收缩力受损;但是，EDL和DIA肌肉受到的影响比SOL肌肉受到的影响更大。光谱学结果还显示，辛伐他汀治疗的肌肉中蛋白质，糖原，核酸，脂质含量降低，脂质顺序和脂质动力学增加。脂质顺序和动力学直接影响膜的厚度。因此，膜离子通道的动力学和功能也受到影响，导致他汀类药物引起的肌肉收缩力受损。此外，观察到α-螺旋和β-折叠的减少以及无规卷曲，聚集和反平行的β-折叠的增加，表明蛋白质变性。光谱研究表明，辛伐他汀给药后肌肉中分子结构改变的程度为EDL> DIA> SOL。结论辛伐他汀引起的结构和功能改变在快肌中比在慢肌中更为深刻。一般意义辛伐他汀的肌毒性作用主要在快速抽搐的肌肉中观察到。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号