Heme oxygenase-1 therapy attenuates muscle atrophy following global brachial plexus avulsion in juvenile rats

  • Impact factors: 3.4
  • Publication: MUSCLE & NERVE
  • Author:Hongjiu Qin, Jing Rui, Jie Lao
  • DOI citation-doi:10.1002/mus.27972
  • Date:2023-09-12

Introduction/Aims Brachial plexus injury can seriously affect distal target muscle function, and long-term denervation leads to irreversible structural damage. In the present study, we examined the effect of hemin, a heme oxygenase-1 (HO-1) inducer, on intrinsic forepaw muscle atrophy induced by pan-plexus injury in juvenile rats, as well as its underlying mechanism. Methods A global brachial plexus avulsion (GBPA) model of rat was established, and thirty 6-wk-old male rats were randomly divided into five groups: control, GBPA plus scramble small intering RNA (siRNA), GBPA plus scramble siRNA plus hemin, GBPA plus HO-1 siRNA, and GBPA plus HO-1 siRNA plus hemin. Hemin (50 mg/kg) was administered intraperitoneally once daily and the siRNA (5 μg) was injected intramuscularly twice a week. Intrinsic forepaw muscles were used for analysis. Myofiber cross-sectional area (CSA), capillary-to-fiber ratio (C/F), and fiber-type composition were assessed. The levels of inflammatory factors, ubiquitin-protein ligases, and autophagy-related proteins were also measured. Results We found that hemin treatment could effectively ameliorate denervated intrinsic forepaw muscle atrophy and suppress type I to II myofiber-type conversion. Hemin treatment failed to prevent muscle capillary loss after denervation. The levels of inflammatory factors (tumor necrosis factor alpha [TNFα] and interleukin 6 [IL-6]), ubiquitin-protein ligases (MuRF-1 and MAFbx), and autophagy-related proteins (BNIP3 and LC3B-II/I ratio) were increased by denervation and HO-1 therapy attenuated the increment. Discussion Upregulation of HO-1 might potentially be an effective strategy to alleviate denervation-related muscle atrophy and might be a promising adjunctive treatment to improve hand function in children with pan-plexus injury.

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