Gorospe J R, Tharp M D, Hinckley J, Kornegay J N, Hoffman E P
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, PA 15261.
J Neurol Sci. 1994 Mar;122(1):44-56. doi: 10.1016/0022-510x(94)90050-7.
Dystrophin deficiency has been shown to be the underlying cause of Duchenne muscular dystrophy. Although dystrophin-deficient homologous animal models have been identified (dog, mouse, and cat), the clinical expression of the biochemical defect is species-specific. Thus, while the genetics and biochemistry of Duchenne dystrophy is understood, the pathophysiological cascade leading to muscle weakness in only humans and dogs remains obscure. To begin to dissect the pathophysiology at the histological level, we undertook a systematic study of mast cells in normal and dystrophin-deficient muscle. Mast cells have been implicated in the development of fibrosis in other disorders, and progressive fibrosis has been hypothesized to mediate the failure of muscle regeneration in human and dog dystrophin deficiency. Our results show a strong correlation between mast cell content and localization, and the clinico-histopathological progression in humans, dogs and mice. The mast cell increases were disease specific: other dystrophic myopathies with normal dystrophin generally did not show substantial increases in mast cell content or degranulation. Our data suggest that mast cell accumulation and degranulation may cause the grouped necrosis characteristic of dystrophin deficiency in all species.
肌营养不良蛋白缺乏已被证明是杜氏肌营养不良症的根本原因。尽管已鉴定出缺乏肌营养不良蛋白的同源动物模型（狗、小鼠和猫），但生化缺陷的临床表现在物种间具有特异性。因此，虽然杜氏肌营养不良症的遗传学和生物化学已为人所知，但仅在人类和狗中导致肌肉无力的病理生理级联反应仍不清楚。为了在组织学水平上剖析病理生理学，我们对正常和缺乏肌营养不良蛋白的肌肉中的肥大细胞进行了系统研究。肥大细胞与其他疾病中纤维化的发展有关，并且有人提出进行性纤维化介导人类和狗肌营养不良蛋白缺乏时肌肉再生的失败。我们的结果显示肥大细胞含量和定位与人类、狗和小鼠的临床组织病理学进展之间存在密切相关性。肥大细胞的增加具有疾病特异性：其他肌营养不良蛋白正常的营养不良性肌病通常不会出现肥大细胞含量或脱颗粒的显著增加。我们的数据表明，肥大细胞的积累和脱颗粒可能导致所有物种中肌营养不良蛋白缺乏所特有的成组坏死。
