Inflammation and apoptosis accelerate progression to irreversible atrophy in denervated intrinsic muscles of the hand compared with biceps: proteomic analysis of a rat model of obstetric brachial plexus palsy  

作　　者：Xiao-Heng Yu Ji-Xin Wu Liang Chen Yu-Dong Gu 

机构地区：[1]Department of Hand Surgery,Huashan Hospital and Institutes of Biomedical Sciences,Fudan University,Shanghai,China [2]Shanghai Key Laboratory of Peripheral Nerve and Microsurgery,Shanghai,China

出　　处：《Neural Regeneration Research》2020年第7期1326-1332,共7页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.816019591003263(to JXW);the National Basic Research Program of China(973 Program),No.2014CB542203(to LC)

摘　　要：In treating patients with obstetric brachial plexus palsy,we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps.In a rat model of obstetric brachial plexus palsy,denervated intrinsic musculature of the forepaw entered the irreversible atrophy far earlier than denervated biceps.In this study,isobaric tags for relative and absolute quantitation were examined in the intrinsic musculature of forepaw and biceps on denervated and normal sides at 3 and 5 weeks to identify dysregulated proteins.Enrichment of pathways mapped by those proteins was analyzed by Kyoto Encyclopedia of Genes and Genomes analysis.At 3 weeks,119 dysregulated proteins in denervated intrinsic musculature of the forepaw were mapped to nine pathways for muscle regulation,while 67 dysregulated proteins were mapped to three such pathways at 5 weeks.At 3 weeks,27 upregulated proteins were mapped to five pathways involving inflammation and apoptosis,while two upregulated proteins were mapped to one such pathway at 5 weeks.At 3 and 5 weeks,53 proteins from pathways involving regrowth and differentiation were downregulated.At 3 weeks,64 dysregulated proteins in denervated biceps were mapped to five pathways involving muscle regulation,while,five dysregulated proteins were mapped to three such pathways at 5 weeks.One protein mapped to inflammation and apoptotic pathways was upregulated from one pathway at 3 weeks,while three proteins were downregulated from two other pathways at 5 weeks.Four proteins mapped to regrowth and differentiation pathways were upregulated from three pathways at 3 weeks,while two proteins were downregulated in another pathway at 5 weeks.These results implicated inflammation and apoptosis as critical factors aggravating atrophy of denervated intrinsic muscles of the hand during obstetric brachial plexus palsy.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Fudan University,China(approval No.DF-325)in January 2015.In treating patients with obstetric brachial plexus palsy, we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps. In a rat model of obstetric brachial plexus palsy, denervated intrinsic musculature of the forepaw entered the irreversible atrophy far earlier than denervated biceps. In this study, isobaric tags for relative and absolute quantitation were examined in the intrinsic musculature of forepaw and biceps on denervated and normal sides at 3 and 5 weeks to identify dysregulated proteins. Enrichment of pathways mapped by those proteins was analyzed by Kyoto Encyclopedia of Genes and Genomes analysis. At 3 weeks, 119 dysregulated proteins in denervated intrinsic musculature of the forepaw were mapped to nine pathways for muscle regulation, while 67 dysregulated proteins were mapped to three such pathways at 5 weeks. At 3 weeks, 27 upregulated proteins were mapped to five pathways involving inflammation and apoptosis, while two upregulated proteins were mapped to one such pathway at 5 weeks. At 3 and 5 weeks, 53 proteins from pathways involving regrowth and differentiation were downregulated. At 3 weeks, 64 dysregulated proteins in denervated biceps were mapped to five pathways involving muscle regulation, while, five dysregulated proteins were mapped to three such pathways at 5 weeks. One protein mapped to inflammation and apoptotic pathways was upregulated from one pathway at 3 weeks, while three proteins were downregulated from two other pathways at 5 weeks. Four proteins mapped to regrowth and differentiation pathways were upregulated from three pathways at 3 weeks, while two proteins were downregulated in another pathway at 5 weeks. These results implicated inflammation and apoptosis as critical factors aggravating atrophy of denervated intrinsic muscles of the hand during obstetric brachial plexus palsy. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Fudan University, China(approval N

关 键 词：APOPTOSIS BICEPS DENERVATION INFLAMMATION intrinsic muscles of the hand irreversible muscle atrophy isobaric tags for relative and absolute quantitation nerve regeneration proteomic rat models reversible muscle atrophy 

分 类 号：R73[医药卫生—肿瘤]