Lima Tiago Barbalho, Ribeiro Alexandre Pinto, Conceição Luciano Fernandes da, Bandarra Marcio, Manrique Wilson Gomez, Laus José Luiz
Department of Medicine and Surgery, College of Agricultural and Veterinarian Sciences, University of São Paulo, Jaboticabal, SP, Brazil.
Department of Veterinary Clinical Medicine, College of Veterinary and Agricultural Sciences, Federal University of Mato Grosso, Cuiabá, MT, Brazil.
Arq Bras Oftalmol. 2015 Mar-Apr;78(2):67-72. doi: 10.5935/0004-2749.20150019.
To assess the effects of 0.5% ketorolac tromethamine without preservatives on the expression of iNOS and MMP-9 in alkali burn ulcers.
Twelve eyes of 120-day-old male rabbits were treated (TG) every 6 h with 0.5% ketorolac tromethamine and 12 other eyes were treated with saline solution (CG), immediately after the occurrence of ulcers by 1 M sodium hydroxide (NaOH). Re-epithelialization was monitored using fluorescein every 6 h. After 24 h, six corneas (n=6) of each group were collected (M1). The others (n=6) were collected after reepithelialization (M2). At both moments, the inflammatory infiltrate and the conditions of the newly formed epithelium were histologically analyzed. iNOS and MMP-9 were evaluated by immunohistochemistry.
Mean epithelialization time in TG was 55 ± 0.84 h. In CG, it was 44 ± 1.06 h (p=0.001). At M1, corneas of TG had lower inflammatory exudation compared with (p <0.001). At M2, TG revealed discrete inflammatory exudation (p>0.05) and lower numbers of epithelial layers compared with CG. The mean iNOS in stromal cells did not differ in TG over both moments compared with CG (p>0.05) At M2, the central corneal region expressed more iNOS in both groups compared with the peripheral region. No significant differences were observed in iNOS scores of epithelial immunostaining between the groups and across M1 and M2 (p=0.69). Epithelial immunostaining scores for MMP-9 did not differ in TG compared with CG (p=0.69). The average immunostaining score of MMP-9 in stromal cells showed no differences between groups or moments. There was no correlation between immunostaining of iNOS and MMP-9 or between the amount of inflammatory cells and immunostaining of iNOS.
Use of 0.5% keratolac tromethamine reduced inflammation and delayed reepithelialization in a cornea alkali burn model without impacting the expression of iNOS or MMP-9.
评估不含防腐剂的0.5% 酮咯酸氨丁三醇对碱烧伤溃疡中诱导型一氧化氮合酶(iNOS)和基质金属蛋白酶-9(MMP-9)表达的影响。
120日龄雄性兔的12只眼睛在1 M氢氧化钠(NaOH)致溃疡后立即每6小时用0.5% 酮咯酸氨丁三醇治疗(治疗组,TG),另外12只眼睛用盐溶液治疗(对照组,CG)。每6小时用荧光素监测角膜上皮再形成情况。24小时后,每组收集6只角膜(n = 6)(M1)。其余(n = 6)在角膜上皮再形成后收集(M2)。在这两个时间点,对炎症浸润和新形成上皮的情况进行组织学分析。通过免疫组织化学评估iNOS和MMP-9。
治疗组角膜上皮再形成的平均时间为55 ± 0.84小时。对照组为44 ± 1.06小时(p = 0.001)。在M1时,治疗组角膜的炎症渗出比对照组少(p <0.001)。在M2时,治疗组炎症渗出不明显(p>0.05),且与对照组相比上皮层数更少。与对照组相比,治疗组基质细胞中iNOS的平均值在两个时间点均无差异(p>0.05)。在M2时,两组中央角膜区域的iNOS表达均高于周边区域。两组之间以及M1和M2之间上皮免疫染色的iNOS评分无显著差异(p = 0.69)。治疗组与对照组相比,MMP-9的上皮免疫染色评分无差异(p = 0.69)。基质细胞中MMP-9的平均免疫染色评分在组间和时间点之间均无差异。iNOS免疫染色与MMP-9免疫染色之间或炎症细胞数量与iNOS免疫染色之间均无相关性。
在角膜碱烧伤模型中,使用0.5% 酮咯酸氨丁三醇可减轻炎症并延迟角膜上皮再形成,但不影响iNOS或MMP-9的表达。