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苯扎氯铵和环孢素局部应用于兔结膜的效果:一项组织形态计量学研究。

Effects of benzalkonium chloride and cyclosporine applied topically to rabbit conjunctiva: a histomorphometric study.

作者信息

Faria Nubia Vanessa Lima de, Sampaio Manuella O Borges de, Viapiana Gabriela N, Seabra Nathália M, Russ Heloisa Helena, Montiani-Ferreira Fabiano, Mello Paulo Augusto Arruda

机构信息

Ophthalmology Department, Universidade Federal de São Paulo, São Paulo, SP, Brazil.

Veterinary Department, Universidade Federal do Paraná, Curitiba, PR, Brazil.

出版信息

Arq Bras Oftalmol. 2019 Jul-Aug;82(4):310-316. doi: 10.5935/0004-2749.20190062. Epub 2019 Apr 29.

Abstract

PURPOSE

Chronic instillation of benzalkonium chloride, a preservative, has inflammatory effects on the ocular surface. However, addition of the anti-inflammatory agent cyclosporine to a therapeutic protocol may mitigate these effects. This study compared the toxic effects of a 0.1% benzalkonium chloride solution and the possible protective effect of 0.05% cyclosporine when applied topically to the rabbit conjunctiva.

METHODS

Fifteen age- and weight-matched, female New Zealand white rabbits were categorized into three groups and treated for 30 consecutive days. Group 1, 2, and 3 - benzalkonium chloride received 0.1% every 24 h, 0.05% cyclosporine every 6 h, and both treatments, respectively. In each rabbit, the left eye was subjected to treatment and the right eye was a control. The rabbits were euthanized at after the experiment. Goblet cells and blood vessels were then enumerated in conjunctival tissues stained with periodic acid-Schiff and hematoxylin-eosin, respectively. Differences between treated and untreated eyes and between groups were compared using the t-test and analysis of variance.

RESULTS

Benzalkonium chloride treatment, with and without cyclosporine, significantly reduced (p≤0.05) in the number of goblet cells in treatment eyes compared with that in respective control eyes. Alternatively, adding cyclosporine to benzalkonium chloride did not prevent the loss of conjunctival goblet cells, and a significant reduction in the number of goblet cells was noted. Benzalkonium chloride-induced significant increase in the number of new blood vessels was mitigated significantly by the addition of cyclosporine.

CONCLUSION

This study demonstrated the magnitude of conjunctival injury caused by chronic instillation of benzalkonium chloride. Although cyclosporine did not mitigate the effects on goblet cells, its addition minimized inflammatory angiogenesis induced by benzalkonium chloride.

摘要

目的

长期滴注防腐剂苯扎氯铵会对眼表产生炎症影响。然而,在治疗方案中添加抗炎药环孢素可能会减轻这些影响。本研究比较了0.1%苯扎氯铵溶液的毒性作用以及0.05%环孢素局部应用于兔结膜时可能的保护作用。

方法

将15只年龄和体重匹配的雌性新西兰白兔分为三组,连续治疗30天。第1组、第2组和第3组分别每24小时接受0.1%苯扎氯铵、每6小时接受0.05%环孢素以及同时接受这两种治疗。每只兔子的左眼接受治疗,右眼作为对照。实验结束后对兔子实施安乐死。然后分别对经高碘酸-希夫染色和苏木精-伊红染色的结膜组织中的杯状细胞和血管进行计数。使用t检验和方差分析比较治疗眼与未治疗眼之间以及各组之间的差异。

结果

与各自的对照眼相比,无论是否添加环孢素,苯扎氯铵治疗均使治疗眼中杯状细胞的数量显著减少(p≤0.05)。另外,在苯扎氯铵中添加环孢素并不能防止结膜杯状细胞的丢失,杯状细胞数量仍显著减少。添加环孢素可显著减轻苯扎氯铵引起的新生血管数量的显著增加。

结论

本研究证明了长期滴注苯扎氯铵所导致的结膜损伤程度。虽然环孢素并未减轻对杯状细胞的影响,但其添加使苯扎氯铵诱导的炎症性血管生成降至最低。

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