Bucolo Claudio, Marrazzo Giuseppina, Platania Chiara Bianca Maria, Romano Giovanni Luca, Drago Filippo, Salomone Salvatore
Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, Medical School, University of Catania, Catania, Italy.
J Pharm Pharmacol. 2014 Jul;66(7):954-60. doi: 10.1111/jphp.12224. Epub 2014 Feb 12.
To evaluate the effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) on retinal vascular leakage, and inflammatory markers in endotoxin-induced uveitis (EIU) in rats.
EIU was induced in rats by lipopolysaccharide (LPS). Topical 0.5% indomethacin, 0.09% bromfenac and 0.1% nepafenac were given before and after LPS. Twenty-four hours after LPS, the animals were euthanized and plasma along with retina were collected to assess prostaglandin-E2 (PGE2 ) and C-reactive protein (CRP) levels using enzyme-linked immunosorbent assay. Retinal vascular leakage was assessed by Evans blue. Molecular modelling was used to evaluate interaction of compounds with cyclooxygenase-2 (COX-2).
All NSAIDs tested significantly prevented PGE2 production with higher effect of indomethacin and bromfenac in comparison with nepafenac. The three drugs did not affect plasma CRP levels. The analysis of retinal vascular leakage revealed a significant (P<0.01) decrease after treatment with indomethacin, but no significant changes were observed after treatment with bromfenac and nepafenac. Indomethacin had a different interaction with COX-2 in comparison with bromfenac and amfenac (active metabolite of nepafenac).
Topical treatment with indomethacin, bromfenac and nepafenac has significant anti-inflammatory effects. However, only indomethacin was able to prevent retinal vascular leakage in LPS-injected rats, likely due to the distinctive molecular mechanism.
评估局部使用非甾体抗炎药（NSAIDs）对大鼠内毒素诱导性葡萄膜炎（EIU）中视网膜血管渗漏及炎症标志物的影响。
通过脂多糖（LPS）诱导大鼠发生EIU。在LPS注射前后分别局部给予0.5%吲哚美辛、0.09%溴芬酸和0.1%奈帕芬酸。LPS注射24小时后，对动物实施安乐死并收集血浆及视网膜，采用酶联免疫吸附测定法评估前列腺素-E2（PGE2）和C反应蛋白（CRP）水平。通过伊文思蓝评估视网膜血管渗漏情况。利用分子建模评估化合物与环氧化酶-2（COX-2）的相互作用。
所有受试NSAIDs均能显著抑制PGE2的产生，其中吲哚美辛和溴芬酸的效果优于奈帕芬酸。这三种药物均不影响血浆CRP水平。视网膜血管渗漏分析显示，吲哚美辛治疗后渗漏显著减少（P<0.01），而溴芬酸和奈帕芬酸治疗后未观察到显著变化。与溴芬酸和奈帕芬酸的活性代谢物安芬酸相比，吲哚美辛与COX-2的相互作用不同。
局部使用吲哚美辛、溴芬酸和奈帕芬酸具有显著的抗炎作用。然而，只有吲哚美辛能够预防LPS注射大鼠的视网膜血管渗漏，这可能归因于其独特的分子机制。
