Melatonin improves muscle function of the dystrophic mdx5Cv mouse, a model for Duchenne muscular dystrophy
Melatonin improves muscle function of the dystrophic mdx5Cv mouse, a model for Duchenne muscular dystrophy
复制标题
DOI：
10.1111/j.1600-079x.2011.00871.x
复制
发表时间：
2011-09-01
影响因子：
10.3
通讯作者：
Dorchies, Olivier M.
中科院分区：
文献类型：
--
作者：
Hibaoui, Youssef;Reutenauer-Patte, Julie;Dorchies, Olivier M.
Duchenne肌营养不良症(DMD)是一种严重的X连锁肌肉萎缩疾病，由细胞骨架蛋白dystrophin缺失引起。除了异常的钙处理，许多研究表明氧化应激在该病的发病机制中起着至关重要的作用。考虑到抗氧化剂在营养不良肌肉结构和功能上提供的令人印象深刻的结果，我们研究了褪黑素是否可以保护DMD的动物模型MDX(5CV)小鼠。雄性MDX(5CV)小鼠每日腹腔注射褪黑素。注射(30毫克/公斤体重)或皮下注射(皮下注射)17/18至28/29日龄期间植入(S)(18或54毫克褪黑素作为Melovine(R)植入物)。治疗结束时记录小腿三头肌等长力。IP地址。治疗可增加MDX(5CV)小鼠的位相收缩张力。S灌胃18 mg/kg和ip 30 mg/kg均能明显改善小鼠的最大强直性张力。治疗。褪黑素使营养不良的肌肉收缩和放松得更快。褪黑素治疗的营养不良小鼠力-频率关系右移。随着肌肉功能的改善，褪黑素降低了血浆肌酸激酶活性，这是肌肉损伤的标志。褪黑素处理增加了总谷胱甘肽的含量，降低了氧化/还原谷胱甘肽的比率，表明肌肉的氧化还原状态较好。根据目前的研究，应进一步考虑褪黑素对DMD患者的治疗潜力。
Duchenne muscular dystrophy (DMD) is a severe X-linked muscle-wasting disease caused by the absence of the cytoskeletal protein dystrophin. In addition to abnormal calcium handling, numerous studies point to a crucial role of oxidative stress in the pathogenesis of the disease. Considering the impressive results provided by antioxidants on dystrophic muscle structure and function, we investigated whether melatonin can protect the mdx(5Cv) mouse, an animal model for DMD. Male mdx(5Cv) mouse pups were treated with melatonin by daily intraperitoneal (i.p.) injection (30 mg/kg body weight) or by subcutaneous (s.c.) implant(s) (18 or 54 mg melatonin as Melovine (R) implants) from 17/18 to 28/29 days of age. Isometric force of the triceps surae was recorded at the end of the treatment. The i.p. treatment increased the phasic twitch tension of mdx(5Cv) mice. The maximal tetanic tension was ameliorated by 18 mg s. c. and 30 mg/kg i.p. treatments. Melatonin caused the dystrophic muscle to contract and relax faster. The force-frequency relationship of melatonin-treated dystrophic mice was shifted to the right. In accordance with improved muscle function, melatonin decreased plasma creatine kinase activity, a marker for muscle injury. Melatonin treatment increased total glutathione content and lowered the oxidized/reduced glutathione ratio, indicating a better redox status of the muscle. In light of the present investigation, the therapeutic potential of melatonin should be further considered for patients with DMD.