Department of Cellular and Molecular Biology, Islamic Azad University, North Tehran Branch, Tehran, Iran.
Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Curr Pharm Des. 2024;30(11):859-867. doi: 10.2174/0113816128284671240214080516.
Formation of adhesion bands is a frequent clinical complication after tendon injury or surgery with limited treatment options. This study investigates the repurposing of Angiotensin-Converting-Enzyme Inhibitor (ACEI) in attenuating post-operative tendon-sheath adhesion bands in an Achilles tendon rat model.
Structural, mechanical, histological, and biochemical characteristics of the Achilles tendons were compared in the presence and absence of oral ACEI (enalapril) using the Achilles tendon adhesion (TA) model in rats. Inflammation and total fibrosis of tendon tissues were compared between groups using molecular investigations along with macroscopic and histological scoring methods.
ACEI significantly alleviated the severity, length, and density of Achilles TAs. Moreover, histopathological changes, recruitment of inflammatory cells, and inflammation were significantly decreased in post-operative tissue samples as quantified with the Moran scoring model. We showed that ACEI treatment elicits a potent anti-fibrotic effect on tendon tissue samples, as illustrated by decreasing the severity and extent of the formed fibrotic tissue and collagen accumulation at the site of surgery when scored either by Tang or Ishiyama grading systems. The H&E staining showed no histopathological changes or damage to the principal organs.
Our results showed that ACEI is a safe and effective therapeutic candidate with potent immunomodulatory and anti-fibrotic features to alleviate surgery-induced development of fibrotic adhesive tissue. However, its efficacy needs to be further validated in clinical studies.
粘连带的形成是肌腱损伤或手术后的一种常见临床并发症,治疗选择有限。本研究探讨血管紧张素转换酶抑制剂(ACEI)在减轻跟腱大鼠模型术后肌腱鞘粘连带中的再利用。
在存在和不存在口服 ACEI(依那普利)的情况下,使用跟腱粘连(TA)模型比较了跟腱的结构、力学、组织学和生物化学特征。通过分子研究以及宏观和组织学评分方法比较了各组肌腱组织的炎症和总纤维化程度。
ACEI 显著减轻了跟腱 TA 的严重程度、长度和密度。此外,术后组织样本中的组织学变化、炎症细胞募集和炎症也明显减少,如 Moran 评分模型定量所示。我们表明,ACEI 治疗对肌腱组织样本具有强大的抗纤维化作用,如通过 Tang 或 Ishiyama 分级系统对形成的纤维化组织的严重程度和程度以及手术部位胶原积累的评分所示。H&E 染色显示主要器官没有组织病理学变化或损伤。
我们的结果表明,ACEI 是一种安全有效的治疗候选药物,具有强大的免疫调节和抗纤维化特性,可减轻手术引起的纤维性粘连组织的形成。然而,其疗效需要在临床研究中进一步验证。