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研究尼达尼布对实验性葡萄膜炎模型的作用。

Investigation of effect of nintedanib in experimental uveitis model.

机构信息

Department of Ophthalmology, Faculty of Medicine, Fırat University, Elazığ, Turkey.

Department of Ophthalmology, Van Training and Research Hospital, Van, Turkey.

出版信息

Cutan Ocul Toxicol. 2022 Mar;41(1):55-59. doi: 10.1080/15569527.2021.2016804. Epub 2021 Dec 14.

DOI:10.1080/15569527.2021.2016804
PMID:34905992
Abstract

PURPOSE

This study aims to investigate the protective efficacy of nintedanib in experimental uveitis induced by endotoxins.

MATERIALS AND METHODS

In this study, 24 Wistar albino rats were randomly divided into three groups: Group I was the healthy control with no uveitis that did not receive any treatment, Group II (sham) group did not receive treatment, and Group III (nintedanib) received oral nintedanib for 10 days. On the 10th day, endotoxin-induced uveitis (EIU) was induced by lipopolysaccharide (LPS) injection in Groups II and III. The clinical activity score was evaluated in all groups at the 24th hour, when uveitis formation was thought to be the most intense after LPS injection. All rats were then killed via anaesthesia. Tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels were measured in their right eyes using the enzyme-linked immunosorbent assay (ELISA) method. Further, histopathological examinations were performed on their left eyes.

RESULTS

For Groups I, II, and III, the IL-6 levels were 30.88 ± 1.79, 36.77 ± 1.21, and 30.93 ± 3.96 mg/pr, respectively, and TNF-α levels were 50.20 ± 3.24, 59.87 ± 2.98, and 50.23 ± 4.83 mg/pr, respectively. IL-6, TNF-α levels and clinical activity score were higher in the sham group compared to the other groups, and it decreased significantly in the treatment group ( < 0.05). Intense inflammatory cell infiltration of the ciliary body, edema and hyperaemia were evident in the sham group compared to the healthy control group ( < 0.05). These pathological findings were significantly decreased in the treatment group compared to the sham group ( < 0.05).

CONCLUSION

Nintedanib may be preferable as a new agent for treating non-infectious uveitis. However, further studies are needed to evaluate its long-term effects, effects on other antiinflammatory pathways, side-effects, and ideal dose optimization.

摘要

目的

本研究旨在探讨尼达尼布对内毒素诱导的实验性葡萄膜炎的保护作用。

材料和方法

本研究将 24 只 Wistar 白化大鼠随机分为三组:第 I 组为无葡萄膜炎的健康对照组,不接受任何治疗;第 II 组(假手术)组不接受治疗;第 III 组(尼达尼布)组接受尼达尼布口服治疗 10 天。第 10 天,第 II 组和第 III 组通过注射脂多糖(LPS)诱导内毒素性葡萄膜炎(EIU)。在 LPS 注射后被认为是葡萄膜炎最严重的第 24 小时,所有组均进行临床活动评分评估。然后,所有大鼠通过麻醉处死。使用酶联免疫吸附试验(ELISA)法测量其右眼肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平。进一步对其左眼进行组织病理学检查。

结果

对于第 I、II 和 III 组,IL-6 水平分别为 30.88 ± 1.79、36.77 ± 1.21 和 30.93 ± 3.96 mg/pr,TNF-α 水平分别为 50.20 ± 3.24、59.87 ± 2.98 和 50.23 ± 4.83 mg/pr。与其他组相比,假手术组的 IL-6、TNF-α 水平和临床活动评分更高,而治疗组则显著降低( < 0.05)。与健康对照组相比,假手术组睫状体有强烈的炎性细胞浸润、水肿和充血( < 0.05)。与假手术组相比,治疗组的这些病理发现明显减少( < 0.05)。

结论

尼达尼布可能是治疗非感染性葡萄膜炎的一种新药物。然而,还需要进一步的研究来评估其长期效果、对其他抗炎途径的影响、副作用和理想剂量优化。

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