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
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
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DOI：
10.4103/1673-5374.272619
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发表时间：
2020-01
影响因子：
6.1
通讯作者：
Xiao-Heng Yu;Ji-xin Wu;Liang Chen;Y. Gu
中科院分区：
文献类型：
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作者：
Xiao-Heng Yu;Ji-xin Wu;Liang Chen;Y. Gu
在治疗产科臂丛神经麻痹的患者中，我们注意到失去神经支配的手的内在肌肉以比失去神经支配的二头肌更快的速度不可逆转地萎缩。在产瘫大鼠模型中，失去神经支配的前爪固有肌肉比失去神经支配的二头肌更早进入不可逆转的萎缩。在这项研究中，在3周和5周时，对失神经和正常侧的前爪和二头肌的固有肌肉组织进行了相对和绝对定量的等压标记，以确定异常调节的蛋白质。通过京都基因百科全书和基因组分析，分析了这些蛋白质定位的途径的富集性。在3周时，前爪失神经固有肌中119个异常蛋白被定位到9条肌肉调节通路，而67个异常蛋白在5周时被定位到3条这样的通路。在3周时，27个上调的蛋白质被定位到五条涉及炎症和凋亡的途径，而在5周时，两条上调的蛋白质被定位到一条这样的途径。在3周和5周时，涉及再生和分化途径的53个蛋白质表达下调。在3周时，失神经支配的二头肌中的异常蛋白被定位到5条涉及肌肉调节的通路，而在5周时，5条异常蛋白被定位到3条这样的通路。在3周时，一个被映射到炎症和凋亡途径的蛋白质被上调，而在5周时，三个蛋白质从另外两个途径被下调。3周时，3条途径中有4个蛋白表达上调，5周时，另一条途径中有2个蛋白表达下调。这些结果表明，炎症和细胞凋亡是产科臂丛神经麻痹时加重失神经支配的手内肌萎缩的关键因素。所有实验程序和方案均经复旦大学实验动物伦理委员会中国(批准号：东风-325)在2015年1月。
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.