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视黄醇棕榈酸酯对大鼠干眼模型损伤后角膜和结膜黏蛋白基因表达的影响。

Effect of Retinol Palmitate on Corneal and Conjunctival Mucin Gene Expression in a Rat Dry Eye Model After Injury.

机构信息

1 Pharmaceutical Research Laboratories No.1, Research and Development Headquarters , Lion Corporation, Kanagawa, Japan .

2 Department of Ophthalmology, Juntendo University Shizuoka Hospital , Shizuoka, Japan .

出版信息

J Ocul Pharmacol Ther. 2017 Jan/Feb;33(1):24-33. doi: 10.1089/jop.2015.0161. Epub 2016 Dec 23.

Abstract

PURPOSE

We examined the wound-healing effect of retinol palmitate (VApal) on mucin gene and protein expressions in a rat dry eye model based on lacrimal gland (LG) resection after injury.

METHODS

The rat dry eye model was prepared by surgical resection of the main LG in male Long-Evans rats. After alkaline injury of the central part of the lower palpebral conjunctiva bilaterally, VApal eye drops at 1,500 IU/mL in one eye and a vehicle in the fellow eye were both administered 6 times a day for 7 days. The expression of mucin gene and protein was analyzed by real-time polymerase chain reaction or enzyme-linked immunosorbent assay in the cornea and conjunctiva of MUC1, MUC4, MUC16, and MUC5AC after 1, 3, (5), and 7 days of treatment with VApal.

RESULTS

Significant decreases in fluorescein-stained areas and rose bengal scores were observed in VApal-treated dry eyes compared with vehicle-treated dry eyes at both 3 (P < 0.05) and 7 days (P < 0.01). Significant increases in corneal rMuc4 and conjunctival rMuc5AC after 1 day (P < 0.01) and conjunctival rMuc16 gene expression after 3 days were observed with VApal treatment (P < 0.05). Furthermore, conjunctival MUC16 expression significantly increased after 3 days of VApal treatment (P < 0.05).

CONCLUSIONS

VApal promoted corneal rMuc4, conjunctival rMuc5AC, and conjunctival rMuc16 gene expression in a rat dry eye model after injury. VApal also promoted conjunctival MUC16 expression. These results indicate that VApal has efficacy in improving keratoconjunctival epithelial damage associated with decreased tear production.

摘要

目的

我们研究了视黄醇棕榈酸酯(VApal)对泪腺(LG)切除后大鼠干眼病模型中粘蛋白基因和蛋白表达的伤口愈合作用。

方法

通过手术切除雄性 Long-Evans 大鼠的主要 LG 制备大鼠干眼病模型。在双侧下睑结膜中央碱性损伤后,一只眼滴用 1500IU/ml 的 VApal 滴眼液,另一只眼滴用对照剂,每天 6 次,共 7 天。用 VApal 治疗 1、3、(5)和 7 天后,通过实时聚合酶链反应或酶联免疫吸附试验分析角膜和结膜中 MUC1、MUC4、MUC16 和 MUC5AC 的粘蛋白基因和蛋白表达。

结果

与对照剂处理的干眼症相比,VApal 处理的干眼症在第 3 天(P<0.05)和第 7 天(P<0.01)时荧光素染色面积和玫瑰红染色评分均显著降低。VApal 处理后第 1 天(P<0.01)角膜 rMuc4 和结膜 rMuc5AC 显著增加,第 3 天结膜 rMuc16 基因表达增加(P<0.05)。此外,VApal 处理后第 3 天结膜 MUC16 表达显著增加(P<0.05)。

结论

VApal 促进了损伤后大鼠干眼病模型中角膜 rMuc4、结膜 rMuc5AC 和结膜 rMuc16 基因的表达,同时还促进了结膜 MUC16 的表达。这些结果表明,VApal 可改善与泪液产生减少相关的角结膜上皮损伤的疗效。

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