Wu Ji-Xin, Chen Liang, Ding Fei, Chen Le-Zi, Gu Yu-Dong
Department of Hand Surgery, Huashan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200040, China.
Shanghai Key Laboratory of Peripheral Nerve and Microsurgery, Shanghai, 200040, China.
J Muscle Res Cell Motil. 2016 Apr;37(1-2):17-25. doi: 10.1007/s10974-016-9442-8. Epub 2016 Feb 22.
In obstetric brachial plexus palsy (OBPP), irreversible muscle atrophy occurs much faster in intrinsic muscles of the hand than in the biceps. To elucidate the mechanisms involved, mRNA expression profiles of denervated intrinsic muscles of the forepaw (IMF) and denervated biceps were determined by microarray using the rat model of OBPP where atrophy of IMF is irreversible while atrophy of biceps is reversible. Relative to contralateral control, 446 dysregulated mRNAs were detected in denervated IMF and mapped to 51 KEGG pathways, and 830 dysregulated mRNAs were detected in denervated biceps and mapped to 52 KEGG pathways. In denervated IMF, 10 of the pathways were related to muscle regulation; six with down-regulated and one with up-regulated mRNAs. The remaining three pathways had both up- and down-regulated mRNAs. In denervated biceps, 13 of the pathways were related to muscle regulation, six with up-regulated and seven with down-regulated mRNAs. Five of the pathways with up-regulated mRNAs were related to regrowth and differentiation of muscle cells. Among the 23 pathways with dysregulated mRNAs, 13 were involved in regulation of neuromuscular junctions. Our results demonstrated that mRNAs expression characteristics in irreversibly atrophic denervated IMF were different from those in reversibly atrophic denervated biceps; dysregulated mRNAs in IMF were associated with inactive pathways of muscle regulation, and in biceps they were associated with active pathways of regrowth and differentiation. Lack of self-repair potential in IMF may be a major reason why atrophy of IMF becomes irreversible much faster than atrophy of biceps after denervation.
在产科臂丛神经麻痹(OBPP)中,手部固有肌的不可逆性肌肉萎缩比肱二头肌发生得更快。为阐明其中涉及的机制,利用OBPP大鼠模型,通过微阵列测定了失神经支配的前爪固有肌(IMF)和失神经支配的肱二头肌的mRNA表达谱,其中IMF的萎缩是不可逆的,而肱二头肌的萎缩是可逆的。相对于对侧对照,在失神经支配的IMF中检测到446个失调的mRNA,并映射到51条KEGG通路,在失神经支配的肱二头肌中检测到830个失调的mRNA,并映射到52条KEGG通路。在失神经支配的IMF中,10条通路与肌肉调节有关;6条通路的mRNA下调,1条通路的mRNA上调。其余3条通路的mRNA既有上调也有下调。在失神经支配的肱二头肌中,13条通路与肌肉调节有关,6条通路的mRNA上调,7条通路的mRNA下调。5条mRNA上调的通路与肌肉细胞的再生和分化有关。在23条mRNA失调的通路中,有13条参与神经肌肉接头的调节。我们的结果表明,不可逆萎缩的失神经支配的IMF中的mRNA表达特征与可逆萎缩的失神经支配的肱二头肌中的不同;IMF中失调的mRNA与肌肉调节的非活性通路相关,而在肱二头肌中它们与再生和分化的活性通路相关。IMF缺乏自我修复潜力可能是其失神经支配后萎缩比肱二头肌萎缩更快变得不可逆的主要原因。