Abstract: AbstractObjectiveOur aim is to study the role of tissue inhibitor of metalloproteinase1 (TIMP1) in progressive muscular dystrophy (PMD). MethodsFrom Apr.2002 to Mar.2003,we examined the expression and cellular localization of TIMP1 protein using biopsied frozen muscle from patients with Duchenne muscular dystrophy(DMD)，Becker muscular dystrophy(BMD)，congenital muscular dystrophy (CMD) by immunohistochemistry，double immunofluorescence and Western blot analysis. ResultsThe results of immunohistochemistry and double immunofluorescence showed that TIMP1 was positive in vascular endothelial cells of normal muscles.Immunohistochemistry and Western blot analysis showed that the staining intensity was distinctly increased in dystrophic muscles of PMD for TIMP1.Double immunofluorescence revealed that TIMP1 strongly expressed in the regenerating muscle fibers，macrophages and macrophage infiltrating necrotic fibers.Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were also positive for TIMP1. ConclusionThe elevated local production of TIMP1 in diseased muscles of PMD and their distinct distribution pattern provide evidence that TIMP1 may participate in the pathogenesis of PMD.

Key words: Tissue inhibitor of metalloproteinase1

摘要： 目的探讨金属蛋白酶组织抑制剂1(TIMP1)在进行性肌营养不良(PMD)发病中的作用。 方法中国医科大学附属第一医院等单位于2002年4月至2003年3月，借助免疫组织化学、双免疫荧光标记和Western印迹分析的方法，检测Duchenne型肌营养不良(DMD)、Becker型肌营养不良(BMD)和先天性肌营养不良(CMD)患儿活检肌肉标本中TIMP1的表达和细胞定位。 结果免疫组织化学和双免疫荧光标记结果显示TIMP1在正常肌肉的血管内皮细胞处表达；免疫组织化学和Western印迹分析均显示在PMD萎缩的肌肉中TIMP1的表达明显增强；双免疫荧光标记进一步显示TIMP1在再生肌肉纤维、巨噬细胞和巨噬细胞浸润的坏死纤维中明显表达，DMD和CMD肌肉中的肌内膜和肌束膜中某些激活的成纤维细胞也强烈表达TIMP1。 结论在PMD病变部位TIMP1产生增多及其分布类型提示TIMP1可能参与了PMD的发病。

关键词: 肌营养不良, 金属蛋白酶组织抑制剂1