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土霉素的药理学替代物作为马驹弯曲肢体畸形潜在治疗方法的初步体外细胞活力和增殖研究。

Pharmacological alternatives to oxytetracycline as potential treatment of flexural limb deformities in foals: a preliminary in vitro cell viability and proliferation study.

作者信息

Cardinaux Emmanuel Mathieu, Oltmanns Hilke, Beineke Andreas, Meißner Jessica, Geburek Florian

机构信息

Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.

Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.

出版信息

Sci Rep. 2025 May 6;15(1):15762. doi: 10.1038/s41598-025-00311-z.

Abstract

Flexural limb deformities are a widespread condition in foals. Oxytetracycline is a common conservative treatment option with relaxing effects on the muscle-tendon-unit, potentially mediated through a matrix-metalloproteinase (MMP)-inhibitor mechanism. Its high therapeutic dose for this indication, potential negative side effects, and the guidelines for prudent use of antimicrobials make investigating alternatives desirable. In this study, the influence of substances with potentially similar mechanisms of action, however without antimicrobial properties, on viability and proliferation of juvenile myofibroblasts was assessed in vitro. Myofibroblasts from forelimb superficial digital flexor tendons and accessory ligaments of the deep digital flexor tendon from 6 foals, euthanized for reasons unrelated to this study, were cultured and characterized. The myofibroblasts were incubated with oxytetracycline, the MMP-inhibitors incyclinide, ilomastat, aprotinin, pentoxifylline, the lathyrogenic agent β-aminopropionitrile fumarate and Dulbecco's modified eagle medium as control. Colorimetric cell viability (MTS) and crystal violet assays assessed their viability and proliferation capacities. The morphology and immunohistochemistry profile of the cultured cells was consistent with tendon and ligament myofibroblasts. All test substances were biocompatible, shown by the absence of significant differences with cells incubated with medium, demonstrating the absence of cytotoxic or anti-proliferative effect on juvenile myofibroblasts in the tested concentrations in this preliminary study.

摘要

弯曲肢体畸形在幼驹中是一种普遍存在的病症。土霉素是一种常见的保守治疗选择,对肌腱单位具有松弛作用,可能是通过基质金属蛋白酶(MMP)抑制机制介导的。其针对该适应症的高治疗剂量、潜在的负面副作用以及抗菌药物谨慎使用指南使得研究替代药物成为必要。在本研究中,体外评估了具有潜在相似作用机制但无抗菌特性的物质对幼年肌成纤维细胞活力和增殖的影响。从6匹因与本研究无关的原因实施安乐死的幼驹的前肢浅屈肌腱和深屈肌腱副韧带中获取肌成纤维细胞,进行培养和特性鉴定。将肌成纤维细胞与土霉素、MMP抑制剂英西环肽、伊洛马司他、抑肽酶、己酮可可碱、致跛行剂富马酸β-氨基丙腈以及作为对照的杜氏改良伊格尔培养基一起孵育。比色法细胞活力(MTS)和结晶紫试验评估了它们的活力和增殖能力。培养细胞的形态和免疫组织化学特征与肌腱和韧带肌成纤维细胞一致。所有测试物质均具有生物相容性,与用培养基孵育的细胞相比无显著差异,表明在本初步研究的测试浓度下,对幼年肌成纤维细胞无细胞毒性或抗增殖作用。

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