ACE、AT1受体及TGF-β1在肌营养不良中的表达

Expression of tissue ACE,AT1 receptor and TGF-β1 in muscular dystrophy

目的:探讨肾素-血管紧张素系统(RAS)和转化生长因子β1(TGF-β1)在肌营养不良(MD)中的表达及与肌肉纤维化的关系。方法:应用Western印迹分析和三免疫荧光标记检测杜氏肌营养不良(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)、血管紧张素Ⅱ(AngⅡ)1型(AT1)受体和TGF-β1的表达及共同定位。结果:Western印迹分析结果显示在MD的萎缩肌肉中ACE、AT1受体和TGF-β1的免疫反应明显增强;三免疫荧光标记显示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TGF-β1,ACE和TGF-β1在萎缩肌肉内也共同定位。结论:病变局部ACE、AT1受体和TGF-β1表达增加,表明肌肉组织中RAS在MD时被激活,可能与TGF-β1共同参与MD的发病,并在肌肉纤维化中起重要作用。

Objective：To study the contributive role of the muscle rennin-angiotensin system（RAS） and transforming growth factor-beta1（TGF-β1） in the muscular dystrophy（MD） and relationship with muscle fibrosis.Methods：The expression and cellular localization of angiotensin-converting enzyme（ACE）,angiotensinⅡ（AngⅡ） type 1（AT1） receptor and TGF-β1 protein were determined in biopsied frozen muscle from patients with Duchenne muscular dystrophy（DMD）,Becker muscular dystrophy（BMD）,congenital muscular dystrophy（CMD） by triple immunofluorescence and Western Blot analysis.Results：The immunoreactivity was distinctly increased in MD for ACE,AT1 receptor and TGF-β1.Triple immunolabeling revealed that most activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were positive for ACE and TGF-β1,and ACE was colocalized primarily with TGF-β1.Conclusion：Increased local ACE and AT1 receptor expression shows that muscular tissue RAS is activated in muscular dystrophy,which could play a role in the pathogenesis of MD together with TGF-β1,ACE and TGF-β1 may be important for muscle fibrosis.