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

• Published in: Muscle & nerve 2023-11, Vol.68 (5), p.789-797
• Main Authors: Qin, Hongjiu, Rui, Jing, Lao, Jie
• Format: Article
• Language: English
• Subjects: Atrophy; Autophagy; BNIP3 protein; Brachial plexus; Denervation; Heme oxygenase (decyclizing); Hemin; Immunotherapy; Inflammation; Injuries; Interleukin 6; Muscles; Proteins; siRNA; Structural damage; Tumor necrosis factor-α; Ubiquitin
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.27972

Introduction/AimsBrachial 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.MethodsA 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.ResultsWe 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.DiscussionUpregulation 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.