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评价二十二碳六烯酸在 1 型胶原酶诱导的实验性跟腱病大鼠模型中的保护作用中的细胞因子。

Evaluation of cytokines in protective effect of docosahexaenoic acid in experimental achilles tendinopathy rat model induced with type-1 collagenase.

机构信息

Department of Orthopedics and Traumatology, Denizli State Hospital, Denizli, Turkey.

Department of Physiology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.

出版信息

Connect Tissue Res. 2022 Jul;63(4):393-405. doi: 10.1080/03008207.2021.1982915. Epub 2021 Oct 6.

Abstract

BACKGROUND

We aimed to investigate the effectiveness of docosahexaenoic acid (DHA) as a treatment for Achilles tendinopathy (AT) induced with type-I collagenase in rats and compare it with collagen.

METHODS

The AT model was induced with type I collagenase, and animals were randomly assigned to groups. Group 1:AT, Group 2: Collagen (7.2 mg/kg/day), Group 3:DHA (300 mg/kg/day), and Group 4:DHA (100 mg/kg/day). Right tendons of Group1 were used as a healthy control (HC). Oral treatments were applied for eight weeks. Serum tumor necrosis factor-alpha(TNF-α), matrix metalloproteinase-13 (MMP-13), and interleukin-1 beta(IL-1β) concentrations were determined by ELISA. Tendon samples were taken for histopathological evaluation and examined immunohistochemically with antibodies specific for Col1A1, TNF-α, MMP-13, IL-1β, and nitric oxide synthase-2(NOS-2). The ultimate tensile force (UTF) yield force(YF) and stiffness were measured by biomechanical assessments.

RESULTS

UTF,YF and stiffness values were increased in all treatment groups compared to the AT control, a significant increase was found in Group 2 (p < 0.05). There was severe degeneration of tendon cells in the AT control. The tendon cells in samples from Groups 2-3 were less degraded, and this was statistically significant (p < 0.05). TNF-α, MMP-13, IL-1β, and NOS-2 expressions were significantly higher in the AT control compared to the HC. In all treatment groups, their concentrations were lower than in the AT control. Serum TNF-α, MMP-13, and IL-1β levels were lower in all treatment groups (Especially in Group3 (p < 0.001)) compared to Group1.

CONCLUSION

The efficacy of high-dose DHA as a treatment for AT was investigated from biochemical, histopathological, and biomechanical perspectives. The results showed that DHA could be an alternative treatment compound to collagen.

摘要

背景

本研究旨在探讨二十二碳六烯酸(DHA)治疗大鼠 I 型胶原酶诱导的跟腱病(AT)的疗效,并与胶原进行比较。

方法

采用 I 型胶原酶诱导 AT 模型,动物随机分组。第 1 组:AT 组;第 2 组:胶原(7.2mg/kg/天);第 3 组:DHA(300mg/kg/天);第 4 组:DHA(100mg/kg/天)。第 1 组右侧跟腱作为健康对照组(HC)。给予口服治疗 8 周。采用酶联免疫吸附试验(ELISA)测定血清肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-13(MMP-13)和白细胞介素-1β(IL-1β)浓度。取肌腱标本进行组织病理学评估,并采用 Col1A1、TNF-α、MMP-13、IL-1β和一氧化氮合酶-2(NOS-2)特异性抗体进行免疫组织化学检查。通过生物力学评估测量最大拉伸力(UTF)屈服力(YF)和刚度。

结果

与 AT 对照组相比,所有治疗组的 UTF、YF 和刚度值均增加,第 2 组有显著增加(p<0.05)。AT 对照组的肌腱细胞严重退化。第 2-3 组的肌腱细胞降解程度较低,差异有统计学意义(p<0.05)。与 HC 相比,AT 对照组的 TNF-α、MMP-13、IL-1β和 NOS-2 表达显著升高。所有治疗组的浓度均低于 AT 对照组。与第 1 组相比,所有治疗组的血清 TNF-α、MMP-13 和 IL-1β 水平均降低(尤其是第 3 组(p<0.001))。

结论

从生化、组织病理学和生物力学角度探讨了高剂量 DHA 治疗 AT 的疗效。结果表明,DHA 可能是胶原的替代治疗化合物。

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