PDF(Pubmed)
Abstract：
Tendinopathy is a prevalent condition in orthopedics patients, exerting a profound impact on tendon functionality. However, its underlying mechanism remains elusive and the efficacy of pharmacological interventions continues to be suboptimal. Verapamil is a clinically used medicine with anti-inflammation and antioxidant functions. This investigation aimed to elucidate the impact of verapamil in tendinopathy and the underlying mechanisms through which verapamil ameliorates the severity of tendinopathy. In in vitro experiments, primary tenocytes were exposed to interleukin-1 beta (IL-1β) along with verapamil at a concentration of 5 μM. In addition, an in vivo rat tendinopathy model was induced through the localized injection of collagenase into the Achilles tendons of rats, and verapamil was injected into these tendons at a concentration of 5 μM. The in vitro findings highlighted the remarkable ability of verapamil to attenuate extracellular matrix degradation and apoptosis triggered by inflammation in tenocytes stimulated by IL-1β. Furthermore, verapamil was observed to significantly suppress the inflammation-related MAPK/NFκB pathway. Subsequent investigations revealed that verapamil exerts a remediating effect on mitochondrial dysfunction, which was achieved through activation of the Nrf2/HO-1 pathway. Nevertheless, the protective effect of verapamil was nullified with the utilization of the Nrf2 inhibitor ML385. In summary, the in vivo and in vitro results indicate that the administration of verapamil profoundly mitigates the severity of tendinopathy through suppression of inflammation and activation of the Nrf2/HO-1 pathway. These findings suggest that verapamil is a promising therapeutic agent for the treatment of tendinopathy, deserving further and expanded research.
摘要：
肌腱病是骨科患者的常见病,对肌腱功能产生深远的影响。然而,其潜在的机制仍然难以捉摸，药物干预的疗效仍然欠佳。维拉帕米是临床上使用的具有抗炎和抗氧化功能的药物。这项研究旨在阐明维拉帕米对肌腱病的影响以及维拉帕米改善肌腱病严重程度的潜在机制。在体外实验中,将原代肌腱细胞暴露于浓度为5μM的白介素-1β（IL-1β）和维拉帕米。此外,通过向大鼠跟腱局部注射胶原酶诱导体内大鼠肌腱病模型，并将维拉帕米以5μM的浓度注射到这些肌腱中。体外发现强调了维拉帕米减弱IL-1β刺激的肌腱细胞炎症引发的细胞外基质降解和凋亡的显着能力。此外，观察到维拉帕米显著抑制炎症相关的MAPK/NFκB通路。随后的研究表明，维拉帕米对线粒体功能障碍具有治疗作用，这是通过激活Nrf2/HO-1途径实现的。然而，使用Nrf2抑制剂ML385后，维拉帕米的保护作用无效。总之,体内和体外结果表明，维拉帕米的给药通过抑制炎症和激活Nrf2/HO-1途径，大大减轻了肌腱病的严重程度。这些发现表明，维拉帕米是治疗肌腱病的一种有前途的治疗剂，值得进一步扩大研究。
