Kong Jie, Yang Liqing, Li Qiuling, Cao Jiqing, Yang Juan, Chen Fei, Wang Yanyun, Zhang Cheng
The First Affiliated Hospital, Sun Yet-sen University, Guangdong Province, People's Republic of China.
Neuroreport. 2012 Jan 25;23(2):82-7. doi: 10.1097/WNR.0b013e32834e7e54.
Duchenne muscular dystrophy is the most common genetic muscle disease. Affected muscles are characterized by abnormal acetylcholine receptor (AChR) clustering. Some studies have suggested that changes in AChR clusters are secondary to degenerative processes. In this study, we demonstrate that AChR cluster fragmentation and muscle degeneration are separate events. We compared AChR clusters and pathological features in mdx mice (mutated dystrophin) and dko mice (mutated dystrophin and utrophin). AChR clusters were identified by binding with α-bungarotoxin, and pathological features were observed by classical immunohistochemical techniques. AChR clusters in mdx and dko mice were reduced in number and exhibited structural fragmentation. However, AChR cluster fragmentation was not significantly different in mdx and dko mice, although more severe inflammatory infiltration and degeneration were observed in dko mice. Furthermore, neuronal nitric oxide synthase, which interacts with dystrophin to anchor itself at the sarcolemma, was notably reduced in mdx and dko mice. Fragmentation of AChR and muscle degeneration are separate events, and both are secondary results of destabilization on the sarcolemma and the cytoskeleton.
杜兴氏肌肉营养不良症是最常见的遗传性肌肉疾病。受影响的肌肉的特征是乙酰胆碱受体（AChR）簇异常。一些研究表明，AChR簇的变化是退化过程的继发结果。在本研究中，我们证明AChR簇的碎片化和肌肉退化是独立的事件。我们比较了mdx小鼠（肌营养不良蛋白突变）和dko小鼠（肌营养不良蛋白和抗肌萎缩蛋白均突变）的AChR簇和病理特征。通过与α-银环蛇毒素结合来鉴定AChR簇，并通过经典免疫组织化学技术观察病理特征。mdx和dko小鼠中的AChR簇数量减少且呈现结构碎片化。然而，mdx和dko小鼠的AChR簇碎片化没有显著差异，尽管在dko小鼠中观察到更严重的炎症浸润和退化。此外，与肌营养不良蛋白相互作用以将自身锚定在肌膜上的神经元型一氧化氮合酶在mdx和dko小鼠中显著减少。AChR的碎片化和肌肉退化是独立的事件，并且两者都是肌膜和细胞骨架不稳定的继发结果。
