Nazari Seyedeh Elnaz, Ghorbani Elnaz, Al-Asady Abdulridha Mohammed, Sayyed-Hosseinian Sayyed-Hadi, Rahmani Farzad, Vahedi Ehsan, Avan Amir, Askarnia-Faal Mohammad-Mostafa, Naimi Hamideh, Khazaei Majid, Hassanian Seyed Mahdi
Department of Medical Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Medical Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Med Sci. 2025 Aug 1;50(8):570-580. doi: 10.30476/ijms.2025.102711.3587. eCollection 2025 Aug.
Peritendinous adhesion as a common post-surgical complication usually occurs as a result of a large portion of sports and hard job-related injuries. This study aims to evaluate the repurposed potential of the immunosuppressive approved drug, tacrolimus, in decreasing adhesion band formation post-Achilles tendon surgeries in an animal model.
Rats were randomly assigned to four groups control, sham with surgical intervention but no adhesion, positive control group with surgical transection and adhesion received no treatment, tacrolimus group was the same as the positive control group except that rats were treated with 2 mg/Kg/day tacrolimus orally for 21 days. The anti-inflammatory and fibrinolytic properties of oral tacrolimus treatment in attenuating the formation of adhesion bands were analyzed by One-way ANOVA or the Kruskal-Wallis test.
Tacrolimus decreased the length (P=0.001), density (P=0.001), grading (P=0.023), severity (P=0.001), and thickness (P=0.008) of post-surgical adhesion bands compared to the untreated group. Histopathological changes and recruitment of inflammatory cells to the tendon tissue sections were attenuated in the tacrolimus-treated group (P=0.001) in comparison with the positive control group. Compared to the untreated group, tacrolimus treatment decreased the expression of IL-1β (P=0.059) in the tendon tissue, but the difference was not statistically significant. Moreover, tacrolimus elicited anti-fibrotic responses by reducing the expression of tissue growth factor-β (TGF-β) in the tendon and inhibiting collagen deposition, fibrosis quantity (P=0.001), fibrosis grading (P=0.001), and total fibrosis scores (P=0.001), as visualized by Masson's trichrome staining.
These results support the protective properties of tacrolimus in decreasing post-operative adhesion band formation in the animal model.
腱周粘连作为一种常见的术后并发症，通常是由大部分与运动和繁重工作相关的损伤引起的。本研究旨在评估免疫抑制批准药物他克莫司在动物模型中减少跟腱手术后粘连带形成的重新利用潜力。
将大鼠随机分为四组：对照组、接受手术干预但无粘连的假手术组、手术切断并粘连且未接受治疗的阳性对照组、他克莫司组，该组与阳性对照组相同，只是大鼠口服2mg/Kg/天的他克莫司，持续21天。通过单因素方差分析或Kruskal-Wallis检验分析口服他克莫司治疗在减轻粘连带形成方面的抗炎和纤溶特性。
与未治疗组相比，他克莫司降低了术后粘连带的长度（P=0.001）、密度（P=0.001）、分级（P=0.023）、严重程度（P=0.001）和厚度（P=0.008）。与阳性对照组相比，他克莫司治疗组的组织病理学变化和炎症细胞向肌腱组织切片的募集减少（P=0.001）。与未治疗组相比，他克莫司治疗降低了肌腱组织中IL-1β的表达（P=0.059），但差异无统计学意义。此外，通过Masson三色染色观察，他克莫司通过降低肌腱中组织生长因子-β（TGF-β）的表达并抑制胶原蛋白沉积、纤维化量（P=0.001）、纤维化分级（P=0.001）和总纤维化评分（P=0.001）引发抗纤维化反应。
这些结果支持他克莫司在动物模型中减少术后粘连带形成的保护作用。
