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利用白介素 1 受体拮抗剂逆转大鼠模型中与既定腱病相关的变化。

The use of an IL1-receptor antagonist to reverse the changes associated with established tendinopathy in a rat model.

机构信息

Department of Orthopaedics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.

出版信息

Scand J Med Sci Sports. 2019 Jan;29(1):82-88. doi: 10.1111/sms.13310. Epub 2018 Oct 15.

Abstract

Interleukin-1 (IL1) is a cytokine that plays a role in inflammation and is a potential contributor to the inflammation present in tendinopathy. Its inhibition may be of use in the treatment of tendinopathy and has been a target for treatment. To evaluate how an IL1-receptor antagonist (IL1-RA) reverses pathologic changes associated with established patellar tendinopathy, we randomized 48 Sprague-Dawley retired breeder rats into three groups having weekly bilateral patellar tendon injections for 6 weeks. The control group received 0.1 mL saline for 6 weeks. The intervention groups were treated with 0.1 mL 2% carrageenan for 4 weeks. Beginning at week three, the IL1-RA group received 0.94 mg of the IL1-RA (2.5 mg/kg) added to the 0.1 mL 2% carrageenan and 0.94 mg of the IL1-RA alone for the final 2 weeks, while the CAR received 0.1 mL saline for the final 2 weeks. Animals were euthanized 6 weeks after initial injection. The CAR group demonstrated significantly (P < 0.05) shorter tendon lengths (7.81 ± 0.44 mm) than the control (8.25 ± 0.58 mm) and IL1-RA (8.34 ± 0.52 mm) group (P < 0.05). Macroscopically, plaque-like formations were reduced and margins of the tendon were more evident in the IL1-RA group compared to the CAR group. CAR group demonstrated significantly greater histopathologic changes (inflammatory cell density, disorganization of collagen, nuclear rounding, and angiogenesis) than the control and IL1-RA group. No significant difference in mechanical properties of the tendon was noted. These findings demonstrate IL1-RA can reduce pathologic changes in the patellar tendon in an established tendonitis model although did not demonstrate a difference in mechanical properties.

摘要

白细胞介素-1 (IL1) 是一种细胞因子,在炎症中发挥作用,是肌腱病中炎症的潜在贡献者。其抑制可能对肌腱病的治疗有用,并且一直是治疗的目标。为了评估白细胞介素 1 受体拮抗剂 (IL1-RA) 如何逆转与已建立的髌腱病相关的病理变化,我们将 48 只斯普拉格-道利退休种鼠随机分为三组,每周双侧髌腱注射 6 周。对照组接受 6 周 0.1ml 生理盐水。干预组用 0.1ml 2%卡拉胶治疗 4 周。从第 3 周开始,IL1-RA 组在最后 2 周内将 0.1ml 2%卡拉胶中添加 0.94mgIL1-RA(2.5mg/kg)和单独添加 0.94mgIL1-RA,而 CAR 组在最后 2 周内接受 0.1ml 生理盐水。初次注射后 6 周处死动物。CAR 组的肌腱长度明显(P<0.05)比对照组(7.81±0.44mm)和 IL1-RA 组(8.34±0.52mm)短(7.81±0.44mm)(P<0.05)。大体上,与 CAR 组相比,IL1-RA 组斑块样形成减少,肌腱边缘更明显。CAR 组的组织病理学变化(炎症细胞密度、胶原排列紊乱、核圆化和血管生成)明显大于对照组和 IL1-RA 组。肌腱力学性能无显著差异。这些发现表明,IL1-RA 可以减少已建立的肌腱炎模型中髌腱的病理变化,尽管在机械性能方面没有差异。

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