Subcutaneous injection, from birth, of epigallocatechin-3-gallate, a component of green tea, limits the onset of muscular dystrophy in mdx mice:: a quantitative histological, immunohistochemical and electrophysiological study
Subcutaneous injection, from birth, of epigallocatechin-3-gallate, a component of green tea, limits the onset of muscular dystrophy in mdx mice:: a quantitative histological, immunohistochemical and electrophysiological study
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DOI：
10.1007/s00418-008-0390-2
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发表时间：
2008-04-01
影响因子：
2.3
通讯作者：
Stoward, Peter J.
中科院分区：
文献类型：
--
作者：
Nakae, Yoshiko;Hirasaka, Katsuya;Stoward, Peter J.
营养不良的肌肉遭受增强的氧化应激。我们已经调查了是否管理的抗氧化剂，表没食子儿茶素-3-没食子酸酯（EGCG），绿色茶的一个组成部分，减少他们的氧化应激和病理生理在mdx小鼠，一个温和的人类杜氏型肌营养不良症的表型模型。在出生后，将EGCG（5 mg/kg体重的盐水溶液）每周4次皮下注射到C57正常和肌营养不良蛋白缺陷型mdx小鼠的背部，持续8周。将生理盐水注射到正常和mdx对照中。EGCG对正常小鼠或mdx小鼠的体重几乎没有可观察到的影响。与此相反，它在血液化学、肌肉组织学和电生理学方面对mdx小鼠产生了以下改善。首先，血清肌酸激酶活性降低至正常水平。第二，荧光脂褐质颗粒的比目鱼肌和膈肌的每单位体积的数量显着减少了约50%的数量相比，在相应的盐水处理的控制。第三，在横膈膜和比目鱼肌部分，组织学正常的肌纤维所占的相对面积显着增加1.5至2倍，而结缔组织和坏死的肌纤维的相对面积大幅减少。第四，比目鱼肌最大强直力下降一半的时间增加到接近正常值。第五，膈肌中utrophin的量显著增加了17%，部分补偿了肌营养不良蛋白表达的缺乏。
Dystrophic muscles suffer from enhanced oxidative stress. We have investigated whether administration of an antioxidant, epigallocatechin-3-gallate (EGCG), a component of green tea, reduces their oxidative stress and pathophysiology in mdx mice, a mild phenotype model of human Duchenne-type muscular dystrophy. EGCG (5 mg/kg body weight in saline) was injected subcutaneously 4x a week into the backs of C57 normal and dystrophin-deficient mdx mice for 8 weeks after birth. Saline was injected into normal and mdx controls. EGCG had almost no observable effects on normal mice or on the body weights of mdx mice. In contrast, it produced the following improvements in the blood chemistry, muscle histology, and electrophysiology of the treated mdx mice. First, the activities of serum creatine kinase were reduced to normal levels. Second, the numbers of fluorescent lipofuscin granules per unit volume of soleus and diaphragm muscles were significantly decreased by about 50% compared to the numbers in the corresponding saline-treated controls. Third, in sections of diaphragm and soleus muscles, the relative area occupied by histologically normal muscle fibres increased significantly 1.5- to 2-fold whereas the relative areas of connective tissue and necrotic muscle fibres were substantially reduced. Fourth, the times for the maximum tetanic force of soleus muscles to fall by a half increased to almost normal values. Fifth, the amount of utrophin in diaphragm muscles increased significantly by 17%, partially compensating for the lack of dystrophin expression.