肌营养不良冷冻肌肉标本纤溶酶原激活物抑制物-1的表达

Expression of Plasminogen Activator Inhibitor-1 of Frozen Muscle Specimensin Muscular Dystrophy

目的探讨纤溶酶原激活物抑制物-1(PAI-1)借助于抑制细胞外基质降解在进行性肌纤维化的发展中作用,揭示PAI-1在肌营养不良(MD)中的作用。方法应用免疫组织化学、双免疫荧光标记和Western印迹分析检测5例Duchenne型肌营养不良(DMD)、3例Becker型肌营养不良(BMD)、9例先天性肌营养不良(CMD)和4例正常活检冷冻肌肉标本中PAI-1的表达和细胞定位。结果PAI-1只在正常肌肉的血管内皮细胞处表达。免疫组织化学及Western印迹分析均表明PAI-1在大多数MD的萎缩肌肉中的表达明显高于正常肌肉。双免疫标记显示PAI-1在再生肌纤维的细胞浆和细胞核、巨噬细胞、巨噬细胞浸润的坏死纤维中强烈表达,在DMD和CMD肌肉中的肌内膜和肌束膜中的某些激活的成纤维细胞中明显表达。结论PAI-1在萎缩肌肉中过度表达的作用尚不清楚,但PAI-1在MD病变肌肉的局部表达增强及其明显的分布类型为PAI-1参与MD的病变提供了依据。

Objective To explore the role of pl^sminogen activator inhibitor- Ⅰ （PAI- 1 ）in development of progressive fibrosis via the inhibition of extracellular matrix degradation,and to reveal the contributive role of PAI- Ⅰ in muscular dystrophy （MD）. Methods Expression and cellular localization of PAI- 1 protein were examined in frozen muscle specimens obtained via biopsy from 5 patients with duchenne muscular dystrophy （DMD）, 3 patients with becket muscular dystrophy （BMD）, 9 patients with congenital muscular dystrophy （CMD） and 4 cases with normal muscle by immunohistochemistry, double immunofluorescence and Western blot analysis. Results PAI- 1 was positive only in vascular endothelial cells of normal muscle. Both immunohistochemistry and Western - blot analysis showed that PAI- 1 expression distinctly increased in most dystrophic muscles of MD than that in normal muscles. Double immunolabeling revealed that PAl - 1 strongly expressed in cytoplasm and nuclei of regenerating muscle fibers, macrophages, macrophage infiltrating necrotic fibers. Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were positive for PAI - 1. Conclusions The functional consequence of overexpression of PAI - 1 in dystrophic muscles is unknown but the elevated local expression of PAI - 1 in diseased muscles of MID and their distinct distribution pattern provide evidence that PAI - 1 participate in pathogenesis of MD.