Takemitsu M, Arahata K, Nonaka I
Division of Ultrastructural Research, National Institute of Neuroscience, NCNP.
Rinsho Shinkeigaku. 1990 Oct;30(10):1066-72.
The most ideal therapeutic trial on Duchenne muscular dystrophy (DMD) is a transfer of normal myoblasts into dystrophic muscle which has been attempted on animal models in several institutes. In the process of muscle regeneration, the transferred normal myoblasts are expected to incorporate into the regenerating fibers in host dystrophic mouse. To know the capacity of muscle regeneration in dystrophic muscle, we compared the regenerating process of the normal muscle with that of the dystrophic muscle after myonecrosis induced by 0.25% bupivacaine hydrochloride (BPVC) chronologically. In the present study, C57BL/10ScSn-mdx (mdx) mouse was used as an animal model of DMD and C57BL/10ScSn (B10) mouse as a control. There was no definite difference in the behavior of muscle fiber regeneration between normal and dystrophic muscles. The dystrophic muscle regenerated rapidly at the similar tempo to the normal as to their size and fiber type differentiation. The variation in fiber size diameter of dystrophic muscle, however, was more obvious than that of normal. To promote successful myoblast transfer from B10 mouse into dystrophic mdx mouse at higher ratio, cultured normal myoblasts were transferred into the regenerating dystrophic muscle on the first and the second day after myonecrosis induced by BPVC. Two weeks after the myoblast injection, the muscles were examined with immunohistochemical stain using anti dystrophin antibody. Although dystrophin-positive fibers appeared in dystrophic muscle, the positive fibers were unexpectedly small in number (3.86 +/- 1.50%).(ABSTRACT TRUNCATED AT 250 WORDS)
针对杜氏肌营养不良症(DMD)的最理想治疗试验是将正常成肌细胞移植到营养不良的肌肉中,多个研究机构已在动物模型上进行了此类尝试。在肌肉再生过程中,预期移植的正常成肌细胞会融入宿主营养不良小鼠再生的纤维中。为了解营养不良肌肉的再生能力,我们按时间顺序比较了正常肌肉与经0.25%盐酸布比卡因(BPVC)诱导发生肌坏死的营养不良肌肉的再生过程。在本研究中,C57BL/10ScSn-mdx(mdx)小鼠被用作DMD的动物模型,C57BL/10ScSn(B10)小鼠作为对照。正常肌肉和营养不良肌肉在肌纤维再生行为上没有明显差异。营养不良肌肉的再生速度与正常肌肉相似,在大小和纤维类型分化方面都很快。然而,营养不良肌肉纤维直径的变化比正常肌肉更明显。为了以更高比例促进B10小鼠的正常成肌细胞成功移植到营养不良的mdx小鼠中,在BPVC诱导肌坏死后的第一天和第二天,将培养的正常成肌细胞移植到再生的营养不良肌肉中。成肌细胞注射两周后,使用抗肌营养不良蛋白抗体进行免疫组织化学染色检查肌肉。尽管肌营养不良肌肉中出现了肌营养不良蛋白阳性纤维,但阳性纤维的数量出乎意料地少(3.86 +/- 1.50%)。(摘要截短于250字)