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关节内曲安奈德治疗马复发性关节炎炎症模型的疗效。

Treatment effects of intra-articular triamcinolone acetonide in an equine model of recurrent joint inflammation.

机构信息

UCD School of Veterinary Medicine, University College Dublin, Dublin, Ireland.

Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

出版信息

Equine Vet J. 2021 Nov;53(6):1277-1286. doi: 10.1111/evj.13396. Epub 2020 Dec 30.

DOI:10.1111/evj.13396
PMID:33280164
Abstract

BACKGROUND

Intra-articular triamcinolone acetonide is a widely used treatment for joint inflammation despite limited scientific evidence of its efficacy.

OBJECTIVES

To investigate if intra-articular triamcinolone acetonide has sustained anti-inflammatory effects using an equine model of repeated joint inflammation.

STUDY DESIGN

Randomised controlled experimental study.

METHOD

For three consecutive cycles 2 weeks apart, inflammation was induced in both middle carpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After the first LPS injection only, treatment with 12 mg triamcinolone acetonide (TA) followed in one randomly assigned joint, while the contralateral joint was treated with sterile saline (control). Clinical parameters (composite welfare scores, joint effusion, joint circumference) were recorded and synovial fluid samples were analysed for various biomarkers (total protein, WBCC; PGE ; CCL2; TNFα; MMP; GAGs; C2C; CPII) at fixed timepoints (post injection hours 0, 8, 24, 72 and 168). The effects of time and treatment on clinical and synovial fluid parameters and the presence of time-treatment interactions were tested using a linear mixed model for repeated measures with horse as a random effect, and time and treatment as fixed effects.

RESULTS

The TA treated joints showed significantly higher peak synovial GAG concentrations (Difference in means 283.1875 µg/mL, 95% CI 179.8, 386.6, P < 0.000), and PGE levels (Difference in means 77.8025 pg/mL, 95% CI 21.2, 134.4, P < 0.007) after the first inflammation induction. Significantly lower TP levels were seen with TA treatment after the second induction (Difference in means -7.5 g/L, 95% CI -14.8, -0.20, P < 0.04) . Significantly lower WBCC levels were noted with TA treatment after the first (Difference in means -23.7125 × 10  cells/L, 95% CI -46.7, -0.7, P < 0.04) and second (Difference in means -35.95 × 10  cells/L, 95% CI -59.0, -12.9, P < 0.002) inflammation inductions. Significantly lower general MMP activity was also seen with TA treatment after the second inflammation inductions (Difference in means -51.65 RFU/s, 95% CI -92.4, -10.9, P < 0.01).

MAIN LIMITATIONS

This experimental study cannot fully reflect natural joint disease.

CONCLUSIONS

In this model, intra-articular TA seems to have some anti-inflammatory activity (demonstrated by reductions in TP, WBCC and general MMP activity) up to 2 weeks post treatment but not at 4 weeks. This anti-inflammatory effect appeared to outlast a shorter-lived, potentially detrimental effect illustrated by increased synovial GAG and PGE levels after the first induction.

摘要

背景

尽管关节内曲安奈德治疗关节炎症的疗效的科学证据有限,但它仍被广泛用于治疗关节炎症。

目的

使用马关节炎症的重复诱导模型,研究关节内曲安奈德是否具有持续的抗炎作用。

研究设计

随机对照实验研究。

方法

连续三个周期,每 2 周一次,向 8 匹马的双侧腕中关节注射 0.25ng 脂多糖(LPS)以诱导炎症。在第一次 LPS 注射后,仅在一只随机选择的关节中注射 12mg 曲安奈德(TA),而对侧关节则注射无菌生理盐水(对照)。在固定时间点(注射后 0、8、24、72 和 168 小时)记录临床参数(综合福利评分、关节积液、关节周长),并分析滑膜液样本中的各种生物标志物(总蛋白、白细胞总数;PGE ;CCL2;TNFα;MMP;GAGs;C2C;CPII)。使用马为随机效应的线性混合模型重复测量来测试时间和治疗对临床和滑膜液参数的影响以及时间-治疗相互作用的存在,并且时间和治疗为固定效应。

结果

在第一次炎症诱导后,TA 治疗的关节显示出明显更高的峰值滑膜 GAG 浓度(差异均值 283.1875μg/mL,95%CI 179.8,386.6,P<0.000)和 PGE 水平(差异均值 77.8025pg/mL,95%CI 21.2,134.4,P<0.007)。在第二次诱导后,TA 治疗后 TP 水平明显降低(差异均值 -7.5g/L,95%CI -14.8,-0.20,P<0.04)。在第一次诱导后,TA 治疗后观察到白细胞总数(差异均值 -23.7125×10 个细胞/L,95%CI -46.7,-0.7,P<0.04)和第二次诱导后(差异均值 -35.95×10 个细胞/L,95%CI -59.0,-12.9,P<0.002)白细胞总数明显降低。在第二次炎症诱导后,TA 治疗后也观察到一般 MMP 活性明显降低(差异均值 -51.65RFU/s,95%CI -92.4,-10.9,P<0.01)。

主要局限性

本实验研究不能完全反映自然关节疾病。

结论

在该模型中,关节内 TA 似乎具有一定的抗炎活性(通过降低 TP、白细胞总数和一般 MMP 活性来证明),但在 2 周后治疗后并非在 4 周后。这种抗炎作用似乎超过了第一次诱导后更短暂的、潜在有害的作用,表现为滑膜 GAG 和 PGE 水平升高。

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