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关节内注射倍他米松和曲安奈德在马急性滑膜炎模型中的残留效应。

Residual effects of intra-articular betamethasone and triamcinolone acetonide in an equine acute synovitis model.

机构信息

Department of Veterinary Science, University of Kentucky, Maxwell H. Gluck Equine Research Center, Lexington, Kentucky, USA.

Lincoln Memorial University, Harrogate, Tennessee, USA.

出版信息

Equine Vet J. 2023 Sep;55(5):905-915. doi: 10.1111/evj.13899. Epub 2022 Dec 1.

DOI:10.1111/evj.13899
PMID:36397207
Abstract

BACKGROUND

Intra-articular (IA) corticosteroids are regularly used in equine athletes for the control of joint inflammation.

OBJECTIVES

The goal of this study was to use an acute synovitis inflammation model to determine the residual effects of IA betamethasone and triamcinolone acetonide on various inflammatory parameters and lameness.

STUDY DESIGN

Crossover randomised trial.

METHODS

Five mixed-breed, 2-year-old horses were randomly allocated to an IA treatment of the radiocarpal joint with 9 mg of either betamethasone or triamcinolone acetonide. Two weeks following treatment, horses were injected with 1 μg of lipopolysaccharide (LPS) diluted in 1 ml of saline. Following LPS injection, horses were crossed-over and both sets of injections were repeated after a washout period. Blood samples were collected at multiple time points for mRNA analysis, as well as serum amyloid A (SAA) and cortisol determination. At each time point, lameness was also subjectively scored. Additional injections with saline-only or LPS-only (twice) were conducted as negative and positive controls, respectively. Two-way repeated measures analysis of variance was used to analyse all data.

RESULTS

Corticosteroid-only treatments result in significant mRNA expression differences, as well as significant and prolonged cortisol suppression. Following LPS injection, there was a residual treatment effect with triamcinolone evidenced by a significant treatment effect on IL-6 and PTGS1 (cyclooxygenase-1), lameness, SAA and cortisol concentrations, while only IL-6 expression was affected by betamethasone.

MAIN LIMITATIONS

The acute synovitis model used here results in significant inflammation and is not representative of the low-grade inflammation seen with typical joint disease and residual anti-inflammatory effects may be more profound in naturally occurring joint disease.

CONCLUSIONS

Current regulatory guidelines may be insufficient if the concern is residual anti-inflammatory effects. Additionally, intra-articular corticosteroid administration is not without risk, as evidenced by a significant suppression of serum cortisol concentration and, as such, the benefits of their administration should be weighed against those risks.

摘要

背景

关节内(IA)皮质类固醇经常用于马科运动员,以控制关节炎症。

目的

本研究的目的是使用急性滑膜炎炎症模型来确定 IA 倍他米松和曲安奈德对各种炎症参数和跛行的残留作用。

研究设计

交叉随机试验。

方法

将 5 匹混种、2 岁马随机分配到桡腕关节的 IA 治疗中,接受 9 毫克倍他米松或曲安奈德。治疗后 2 周,马匹注射 1 微克脂多糖(LPS)稀释在 1 毫升盐水中。注射 LPS 后,马匹交叉并在冲洗期后重复两次注射。在多个时间点采集血液样本进行 mRNA 分析,以及血清淀粉样蛋白 A(SAA)和皮质醇测定。在每个时间点,跛行也进行主观评分。单独注射盐水或 LPS(两次)分别作为阴性和阳性对照。使用双向重复测量方差分析分析所有数据。

结果

皮质类固醇单独治疗会导致显著的 mRNA 表达差异,以及显著和持久的皮质醇抑制。注射 LPS 后,曲安奈德仍有残留的治疗作用,表现为 IL-6 和 PTGS1(环氧化酶-1)、跛行、SAA 和皮质醇浓度有显著的治疗作用,而倍他米松仅影响 IL-6 表达。

主要局限性

这里使用的急性滑膜炎模型会导致明显的炎症,与典型关节疾病的低级别炎症不具有代表性,残留的抗炎作用可能在自然发生的关节疾病中更为明显。

结论

如果关注的是残留的抗炎作用,当前的监管指南可能不够充分。此外,关节内皮质类固醇的给药并非没有风险,因为血清皮质醇浓度显著抑制,因此,应该权衡其给药的益处与风险。

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