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在羊脂多糖诱导关节炎模型的开发中进行剂量探索。

Dose-Finding in the Development of an LPS-Induced Model of Synovitis in Sheep.

机构信息

Department of Veterinary Medicine, School of Veterinary Medicine and Animal Science, Federal University of Goiás, Goiânia, Brazil;, Email:

Department of Veterinary Medicine, School of Veterinary Medicine and Animal Science, Federal University of Goiás, Goiânia, Brazil.

出版信息

Comp Med. 2021 Apr 1;71(2):141-147. doi: 10.30802/AALAS-CM-20-000032. Epub 2021 Feb 10.

DOI:10.30802/AALAS-CM-20-000032
PMID:33568256
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8063196/
Abstract

Models of transient synovitis that can be controlled with antiinflammatory and analgesic drugs have been used to study pain amelioration. To this end, we aimed to determine the dose of intraarticularly administered LPS that induced signs of synovitis without systemic signs in clinically healthy male castrated sheep ( = 14). In phase 1, a single dose of LPS (0.5, 1.0, 1.5, or 2.0 ng in a total volume of 0.5 mL) was administered into the right stifle joint. In phase 2, a dose of LPS (1.0 or 2.0 μg) in 0.3 mL was administered to 4 naïve sheep. In phase 3, 4 sheep from phase 1 were inoculated after a 60 d washout period with either 0.5 or 1.0 μg of LPS. During the first 48 h after LPS administration, the following were performed: assessment of clinical parameters; scoring for lameness, pain on limb flexion, and local swelling; and ultrasonography of the joints were performed. The doses tested during phase 1 produced subtle signs. During phase 2, mild to moderate lameness with no evidence of systemic signs occurred at both doses. In phase 3, clinical responses were similar between the 0.5- and 1-μg doses. Signs of swelling were not observed at any time. Therefore, we consider the 0.5-μg to be the most appropriate for this model, because it was the lowest dose tested capable of causing lameness without signs of systemic inflammation in all animals.

摘要

我们曾使用一过性滑膜炎模型(可通过抗炎和镇痛药控制)来研究疼痛缓解。为此,我们旨在确定关节内注射 LPS 的剂量,既能诱导出滑膜炎的迹象,又不引起临床健康去势雄性绵羊(n = 14)出现全身症状。在第 1 阶段,将 0.5 mL 体积中的 0.5、1.0、1.5 或 2.0ng LPS 单次注入右膝关节。在第 2 阶段,4 只未接种的绵羊接受 0.3 mL 中 LPS(1.0 或 2.0μg)的注射。在第 3 阶段,4 只绵羊在 60 天洗脱期后,分别接受 0.5 或 1.0μg LPS 接种。在 LPS 给药后的前 48 小时内,我们进行了以下操作:评估临床参数;跛行评分、肢体弯曲疼痛和局部肿胀评分;并对关节进行超声检查。第 1 阶段测试的剂量仅产生轻微的迹象。在第 2 阶段,两种剂量均出现轻度至中度跛行,且无全身症状的证据。在第 3 阶段,0.5μg 和 1μg 剂量之间的临床反应相似。在任何时候都没有观察到肿胀的迹象。因此,我们认为 0.5μg 是最适合该模型的,因为它是所有动物中引起跛行而不引起全身炎症迹象的最低剂量。

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