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目的揭示肾素一血管紧张素系统(RAS)在肌营养不良(MD)中的作用。方法应用免疫组织化学法、双免疫荧光标记和Western blot分析检测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)患者肌肉活检标本中血管紧张素转移酶(ACE)及血管紧张素Ⅱ(AngⅡ)1型(AT1)受体的表达及细胞定位。结果免疫组织化学和双免疫荧光标记显示正常肌肉的血管内皮细胞为ACE阳性,而AT1受体只在正常肌肉的血管平滑肌细胞中表达。免疫组织化学法和Western blot分析均显示在MD的萎缩肌肉中ACE和AT1受体的免疫反应明显增强,ACE和AT1受体均在再生纤维的膜、细胞浆和细胞核,成纤维细胞,巨噬细胞和巨噬细胞浸润的坏死纤维中强烈表达。双免疫荧光标记显示DMD和CMD肌肉的肌内膜和肌束膜中大多数激活的成纤维细胞表达ACE和AT1受体,特别是AT1更强烈。AT1受体的免疫反应基本与ACE的反应相平行。结论局部ACE和AT1受体表达增加,表明肌肉组织中RAS在MD时被激活,可能在MD的发病中起作用。
Objective To reveal the role of renin-angiotensin system (RAS) in muscular dystrophy (MD). Methods Immunohistochemistry, double immunofluorescence staining and Western blot analysis were used to detect the expression of angiotensin Ⅱ in muscle biopsies of Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and congenital muscular dystrophy (CMD) (ACE) and angiotensin Ⅱ type 1 (AT1) receptor expression and cellular localization. Results Immunohistochemistry and double immunofluorescence labeling showed that the normal muscle of the vascular endothelial cells were ACE positive, while the AT1 receptor was only expressed in normal muscle vascular smooth muscle cells. Immunohistochemistry and Western blot analysis showed that the immunoreactivity of ACE and AT1 receptors was significantly increased in the atrophic muscles of MD. Both ACE and AT1 receptors were localized in the membrane, cytoplasm and nucleus of regenerated fibers, fibroblasts, macrophages Strongly expressed in necrotic fibers infiltrating cells and macrophages. Double immunofluorescence labeling showed that most of the activated fibroblasts in the intima and myofibroblasts of DMD and CMD muscles expressed ACE and AT1 receptors, in particular AT1, more strongly. The AT1 receptor’s immune response is essentially parallel to the ACE reaction. Conclusions The expression of ACE and AT1 receptors in the brain is increased, indicating that RAS in muscle is activated in MD and may play a role in the pathogenesis of MD.