Yalçın Mehmet Burak, Bora Ejder Saylav, Erbaş Oytun
Department of Orthopedics and Traumatology, Bahcelievler Memorial Hospital, Istanbul 34180, Türkiye.
Department of Emergency Medicine, Izmir Atatürk Research and Training Hospital, Izmir 35360, Türkiye.
Curr Issues Mol Biol. 2024 Jan 2;46(1):327-339. doi: 10.3390/cimb46010021.
Peripheral nerve injuries inflict severe consequences, necessitating innovative therapeutic strategies. This study investigates the potential of liraglutide, a glucagon-like peptide-1 receptor agonist, in mitigating the consequences of peripheral nerve injury. The existing treatment methods for such injuries underscore the importance of ongoing translational research efforts. Thirty adult Wistar rats underwent sciatic nerve dissection and repair surgery. The nerves were surgically transected using micro scissors at a precise location located 1.5 cm proximal to the trifurcation site. The study included a control group and two experimental groups, one treated with saline (placebo group) and the other with liraglutide (experimental group) for 12 weeks. Motor function, electromyography (EMG), and biochemical and histopathological analyses were performed after 12 weeks of treatment. Electrophysiological assessments revealed that liraglutide improved the compound muscle action potential (CMAP) amplitude and motor function compared to the saline-treated group. Histological and immunohistochemical analyses demonstrated increased NGF expression, total axon number, and diameter and reduced fibrosis in the liraglutide group. Biochemical analyses illustrated liraglutide's antioxidative properties, evidenced by reduced malondialdehyde (MDA) levels. Galectin-3 levels were suppressed and GDF-11 levels were modulated by liraglutide, indicating anti-inflammatory and anti-apoptotic effects. Liraglutide is a promising therapeutic intervention for peripheral nerve injuries, promoting functional recovery and histopathological improvement. Its multifaceted positive impact, beyond glycemic control, suggests constructive effects on the acute and chronic inflammatory processes associated with peripheral neuropathy. These findings warrant further research to elucidate molecular mechanisms and facilitate clinical translation. The study contributes valuable insights to the growing understanding of GLP-1 receptor agonists' neuroprotective properties in the context of peripheral nerve injuries.
周围神经损伤会造成严重后果,因此需要创新的治疗策略。本研究调查了胰高血糖素样肽-1受体激动剂利拉鲁肽在减轻周围神经损伤后果方面的潜力。此类损伤的现有治疗方法凸显了持续开展转化研究工作的重要性。30只成年Wistar大鼠接受了坐骨神经解剖和修复手术。使用显微剪刀在三叉神经分支点近端1.5厘米处的精确位置将神经切断。该研究包括一个对照组和两个实验组,一组用生理盐水治疗(安慰剂组),另一组用利拉鲁肽治疗(实验组),为期12周。治疗12周后进行运动功能、肌电图(EMG)以及生化和组织病理学分析。电生理评估显示,与生理盐水治疗组相比,利拉鲁肽改善了复合肌肉动作电位(CMAP)幅度和运动功能。组织学和免疫组织化学分析表明,利拉鲁肽组的神经生长因子(NGF)表达增加、轴突总数和直径增加,纤维化减少。生化分析表明利拉鲁肽具有抗氧化特性,丙二醛(MDA)水平降低证明了这一点。利拉鲁肽抑制了半乳糖凝集素-3水平,并调节了生长分化因子11(GDF-11)水平,表明其具有抗炎和抗凋亡作用。利拉鲁肽是一种有前景的周围神经损伤治疗干预措施,可促进功能恢复和组织病理学改善。其多方面的积极影响超出了血糖控制范围,表明对与周围神经病变相关的急慢性炎症过程具有有益作用。这些发现值得进一步研究以阐明分子机制并促进临床转化。该研究为在周围神经损伤背景下对胰高血糖素样肽-1受体激动剂神经保护特性的日益了解提供了有价值的见解。