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0.025%FK-506、0.05%环孢素 A 和 0.3%透明质酸钠滴眼液治疗肉毒杆菌毒素 B 诱导的小鼠干眼症的比较。

Comparison of 0.025% FK-506, 0.05% Cyclosporin A, and 0.3% Sodium Hyaluronate Eye Drops for the Treatment of Botulinum Toxin B-Induced Mouse Dry Eye.

机构信息

1 Guangdong Provincial Hospital of Chinese Medicine , Guangzhou, China .

2 Physical Examination Center, The Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou, China .

出版信息

J Ocul Pharmacol Ther. 2018 Nov;34(9):633-641. doi: 10.1089/jop.2018.0044. Epub 2018 Sep 18.

Abstract

PURPOSE

To compare the effects of FK-506, cyclosporin A (CsA), and sodium hyaluronate (HA) eye drops for the treatment of botulinum toxin B (BTX-B)-induced mouse dry eye.

METHODS

CBA/J mice were randomized into 5 groups. The groups received treatment with eye drops containing 0.025% FK-506 combined with 0.3% HA (FK-506+HA group), 0.025% FK-506 (FK-506 group), 0.05% CsA (CsA group), 0.3% HA (HA group), or 0.9% saline (saline group) 3 days after an intralacrimal gland injection with 20 mU of BTX-B. Tear production, corneal fluorescein staining, blink rate, and the mRNA and protein expression levels of inflammatory cytokines were measured.

RESULTS

FK-506+HA eye drops increased tear production and reduced the corneal fluorescein staining scores at all time points after treatment compared with those in the saline group. Compared with those in the saline group, the tear production and severity of corneal epithelial defects in the FK-506 group were significantly improved at weeks 2 and 4. Compared with the saline eye drops, the CsA eye drops ameliorated only tear production and corneal fluorescein staining scores at week 4 after administration. The FK-506+HA, FK-506, and CsA eye drops downregulated the expression of inflammatory cytokines in both the keratoconjunctival tissues and lacrimal glands at week 4.

CONCLUSIONS

The topical application of 0.025% FK-506 combined with 0.3% HA, 0.025% FK-506, or 0.05% CsA can suppress the expression of inflammatory cytokines and can alleviate the signs of dry eye. Topical application of 0.025% FK-506 combined with 0.3% HA showed the best therapeutic effect and may be a possible therapy for dry eye.

摘要

目的

比较 FK-506、环孢素 A(CsA)和透明质酸钠(HA)滴眼液治疗肉毒毒素 B(BTX-B)诱导的小鼠干眼症的效果。

方法

CBA/J 小鼠随机分为 5 组。在 BTX-B 经泪腺内注射 20mU 后 3 天,各组分别接受含有 0.025%FK-506 联合 0.3%HA(FK-506+HA 组)、0.025%FK-506(FK-506 组)、0.05%CsA(CsA 组)、0.3%HA(HA 组)或 0.9%生理盐水(盐水组)滴眼治疗。测量泪液产生、角膜荧光素染色、眨眼率以及炎症细胞因子的 mRNA 和蛋白表达水平。

结果

与盐水组相比,FK-506+HA 滴眼剂在治疗后所有时间点均增加了泪液产生并降低了角膜荧光素染色评分。与盐水组相比,FK-506 组在第 2 周和第 4 周时泪液产生和角膜上皮缺损的严重程度均显著改善。与盐水滴眼液相比,CsA 滴眼液仅在给药后第 4 周改善了泪液产生和角膜荧光素染色评分。FK-506+HA、FK-506 和 CsA 滴眼剂在第 4 周时下调了角膜结膜组织和泪腺中炎症细胞因子的表达。

结论

局部应用 0.025%FK-506 联合 0.3%HA、0.025%FK-506 或 0.05%CsA 可抑制炎症细胞因子的表达,并可缓解干眼症的体征。局部应用 0.025%FK-506 联合 0.3%HA 显示出最佳的治疗效果,可能是干眼症的一种潜在治疗方法。

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