Dorchies Olivier M, Wagner Stéphanie, Vuadens Ophélie, Waldhauser Katri, Buetler Timo M, Kucera Pavel, Ruegg Urs T
Laboratory of Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences, Univ. of Geneva, Switzerland.
Am J Physiol Cell Physiol. 2006 Feb;290(2):C616-25. doi: 10.1152/ajpcell.00425.2005.
Duchenne muscular dystrophy is a frequent muscular disorder caused by mutations in the gene encoding dystrophin, a cytoskeletal protein that contributes to the stabilization of muscle fiber membrane during muscle activity. Affected individuals show progressive muscle wasting that generally causes death by age 30. In this study, the dystrophic mdx(5Cv) mouse model was used to investigate the effects of green tea extract, its major component (-)-epigallocatechin gallate, and pentoxifylline on dystrophic muscle quality and function. Three-week-old mdx(5Cv) mice were fed for either 1 or 5 wk a control chow or a chow containing the test substances. Histological examination showed a delay in necrosis of the extensor digitorum longus muscle in treated mice. Mechanical properties of triceps surae muscles were recorded while the mice were under deep anesthesia. Phasic and tetanic tensions of treated mice were increased, reaching values close to those of normal mice. The phasic-to-tetanic tension ratio was corrected. Finally, muscles from treated mice exhibited 30-50% more residual force in a fatigue assay. These results demonstrate that diet supplementation of dystrophic mdx(5Cv) mice with green tea extract or (-)-epigallocatechin gallate protected muscle against the first massive wave of necrosis and stimulated muscle adaptation toward a stronger and more resistant phenotype.
杜兴氏肌营养不良症是一种常见的肌肉疾病,由编码抗肌萎缩蛋白的基因突变引起,抗肌萎缩蛋白是一种细胞骨架蛋白,在肌肉活动期间有助于稳定肌纤维膜。受影响的个体表现出进行性肌肉萎缩,通常在30岁前导致死亡。在本研究中,使用营养不良的mdx(5Cv)小鼠模型来研究绿茶提取物、其主要成分(-)-表没食子儿茶素没食子酸酯和己酮可可碱对营养不良肌肉质量和功能的影响。给三周龄的mdx(5Cv)小鼠喂食对照饲料或含有测试物质的饲料1周或5周。组织学检查显示,治疗小鼠的趾长伸肌坏死延迟。在小鼠深度麻醉时记录腓肠肌的力学性能。治疗小鼠的相张力和强直张力增加,达到接近正常小鼠的值。相张力与强直张力的比值得到校正。最后,在疲劳试验中,治疗小鼠的肌肉表现出多30%-50%的残余力。这些结果表明,用绿茶提取物或(-)-表没食子儿茶素没食子酸酯补充营养不良的mdx(5Cv)小鼠的饮食可保护肌肉免受第一波大规模坏死,并刺激肌肉向更强壮、更有抵抗力的表型适应。