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玻璃体内注射甲氨蝶呤治疗兔实验性内毒素诱导性葡萄膜炎

Intra-vitreal injection of methotrexate in experimental endotoxin-induced uveitis in rabbit.

作者信息

Abbaszadeh Hasiri Mohammad, Baghaei Moghaddam Effat, Khalili Mohammad Reza, Hossein Amini Amin, Eghtedari Masoomeh, Azizzadeh Mohammad, Razmi Hooman

机构信息

Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.

Poostchi Ophthalmology Research Center, Department of Ophthalmology, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Vet Res Forum. 2018 Fall;9(4):315-321. doi: 10.30466/vrf.2018.33110. Epub 2018 Dec 15.

DOI:10.30466/vrf.2018.33110
PMID:30713609
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6346491/
Abstract

Uveitis is a major cause of vision loss. Methotrexate (MTX) has been widely used in uveitis due to its relatively safe profile. The purpose of this study was to evaluate the effects of two different dosages of MTX via intra-vitreal administration for treatment of endotoxin induced uveitis (EIU) in an experimental model. Thirty-five healthy rabbits were randomly divided into four groups and all animals were tolerated intra-vitreal injections. The first group received normal saline (NS), the second group received normal saline plus lipopolysaccharide endotoxin (LPS), (NS+LPS), the third group received 400 μg MTX plus LPS (LPS+MTX 400) and the fourth group received 800 μg MTX plus LPS (LPS+MTX 800). Intra-ocular inflammation was evaluated by clinical examination scoring during 7 post-injection days and histopathological examination at the end of study. Kruskal-Wallis and Mann-Whitney U tests were used to compare the histopathological and clinical scores. According to the clinical examinations, all groups demonstrated higher uveitis score than group 1 on first post-injection day. Also, groups 2 and 3 showed greater uveitis score than group 4. On the third, fifth and seventh post-injection days, clinical uveitis score in groups 2, 3 and 4 was significantly higher than group 1. The mean histopathological inflammation intensity scores in groups 2, 3 and 4 were significantly higher than group 1. Single intra-vitreal injection of 400 μg and 800 μg of MTX did not show significant anti-inflammatory effects on EIU in rabbits.

摘要

葡萄膜炎是视力丧失的主要原因。甲氨蝶呤(MTX)因其相对安全的特性已被广泛应用于葡萄膜炎的治疗。本研究的目的是在实验模型中评估两种不同剂量的MTX经玻璃体内注射治疗内毒素诱导性葡萄膜炎(EIU)的效果。35只健康兔子被随机分为四组,所有动物均耐受玻璃体内注射。第一组接受生理盐水(NS),第二组接受生理盐水加脂多糖内毒素(LPS)(NS + LPS),第三组接受400μg MTX加LPS(LPS + MTX 400),第四组接受800μg MTX加LPS(LPS + MTX 800)。在注射后的7天内通过临床检查评分评估眼内炎症,并在研究结束时进行组织病理学检查。使用Kruskal-Wallis和Mann-Whitney U检验比较组织病理学和临床评分。根据临床检查,所有组在注射后的第一天葡萄膜炎评分均高于第一组。此外,第二组和第三组的葡萄膜炎评分高于第四组。在注射后的第三天、第五天和第七天,第二组、第三组和第四组的临床葡萄膜炎评分显著高于第一组。第二组、第三组和第四组的平均组织病理学炎症强度评分显著高于第一组。单次玻璃体内注射400μg和800μg的MTX对兔子的EIU未显示出显著的抗炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f81/6346491/23d73ec9b002/vrf-9-315-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f81/6346491/c07d90a670eb/vrf-9-315-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f81/6346491/ebad7bc70520/vrf-9-315-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f81/6346491/23d73ec9b002/vrf-9-315-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f81/6346491/c07d90a670eb/vrf-9-315-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f81/6346491/ebad7bc70520/vrf-9-315-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f81/6346491/23d73ec9b002/vrf-9-315-g003.jpg

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本文引用的文献

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High Efficacy of Methotrexate in Patients with Recurrent Idiopathic Acute Anterior Uveitis: a Prospective Study.甲氨蝶呤治疗复发性特发性急性前葡萄膜炎患者的高效性:一项前瞻性研究。
Arch Immunol Ther Exp (Warsz). 2017 Feb;65(1):93-97. doi: 10.1007/s00005-016-0402-1. Epub 2016 May 11.
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Diagnosis and classification of autoimmune uveitis.自身免疫性葡萄膜炎的诊断与分类。
Autoimmun Rev. 2014 Apr-May;13(4-5):591-4. doi: 10.1016/j.autrev.2014.01.006. Epub 2014 Jan 12.
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Emerging drugs for the treatment of uveitis.治疗葡萄膜炎的新兴药物。
Expert Opin Emerg Drugs. 2013 Dec;18(4):513-21. doi: 10.1517/14728214.2013.861417.
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Intraocular methotrexate can induce extended remission in some patients in noninfectious uveitis.眼内注射甲氨蝶呤可诱导部分非感染性葡萄膜炎患者获得长期缓解。
Retina. 2013 Nov-Dec;33(10):2149-54. doi: 10.1097/IAE.0b013e31828ac07d.
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Experimental uveitis can be maintained in rabbits for a period of six weeks after a safe sensitization method.实验性葡萄膜炎在安全致敏方法后可在兔子体内维持 6 周。
Curr Eye Res. 2013 Mar;38(3):405-12. doi: 10.3109/02713683.2012.747616. Epub 2013 Jan 7.
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Effect of intravitreal methotrexate and aqueous humor cytokine levels in refractory retinal vasculitis in Behcet disease.眼内注射甲氨蝶呤与房水中细胞因子水平对 Behcet 病难治性视网膜血管炎的影响。
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Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid.叶酸拮抗剂4-氨基蝶酰谷氨酸诱导儿童急性白血病的暂时缓解。
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