丝氨酸蛋白酶抑制剂 A3K 抑制实验性干眼小鼠模型中眼表面鳞状上皮化生的形成。

Serine protease inhibitor A3K suppressed the formation of ocular surface squamous metaplasia in a mouse model of experimental dry eye.

机构信息

Affiliated Xiamen Eye Center and Eye Institute of Xiamen University, Xiamen, China.

Affiliated Xiamen Eye Center and Eye Institute of Xiamen University, Xiamen, China Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China.

出版信息

Invest Ophthalmol Vis Sci. 2014 Aug 7;55(9):5813-20. doi: 10.1167/iovs.13-13546.

DOI:10.1167/iovs.13-13546

PMID:25103264

Abstract

PURPOSE

To investigate the effects and possible mechanisms of serine protease inhibitor A3K (SERPINA3K) on the formation of ocular surface squamous metaplasia in a mouse dry eye model induced by topical benzalkonium chloride (BAC).

METHODS

The eye drops containing SERPINA3K were topically administered during the induction of BAC-induced dry eye. The clinical indications of dry eye were evaluated on day (D)16, including tear break-up time (BUT), tear volume, corneal fluorescein staining, and inflammatory index. Global specimens were collected on D16 and the following examinations were performed: histologic investigation, immunostaining of cytokeratin 10 (K10), p63 and Ki67 in the cornea, and Western blot analysis of tumor necrosis factor-α (TNF-α).

RESULTS

Serine protease inhibitor A3K suppressed the formation of BAC-induced dry eye, presenting with longer BUTs, lower corneal fluorescein staining scores, and inflammatory index, while no significant changes in tear volume. It also reduced the severity of abnormal differentiation and proliferation on ocular surface with lower expressions of K10, p63, and Ki67, and retained the number of goblet cells in the conjunctival fornix. Serine protease inhibitor A3K significantly decreased the levels of TNF-α in the cornea.

CONCLUSIONS

Topical application of SERPINA3K ameliorated the severity of ocular surface squamous metaplasia and suppressed the formation of BAC-induced dry eye.

摘要

目的

研究丝氨酸蛋白酶抑制剂 A3K（SERPINA3K）对苯扎氯铵（BAC）诱导的小鼠干眼模型眼表面鳞状上皮化生形成的影响及可能机制。

方法

在 BAC 诱导的干眼诱导期间局部给予含有 SERPINA3K 的眼药水。在第 16 天（D）评估干眼的临床指征，包括泪膜破裂时间（BUT）、泪液量、角膜荧光素染色和炎症指数。在 D16 收集全球标本，并进行以下检查：组织学检查、角膜中细胞角蛋白 10（K10）、p63 和 Ki67 的免疫染色，以及肿瘤坏死因子-α（TNF-α）的 Western blot 分析。

结果

丝氨酸蛋白酶抑制剂 A3K 抑制了 BAC 诱导的干眼的形成，表现为 BUT 延长、角膜荧光素染色评分和炎症指数降低，而泪液量无明显变化。它还降低了眼表面异常分化和增殖的严重程度，K10、p63 和 Ki67 的表达降低，同时保留了结膜穹窿中的杯状细胞数量。丝氨酸蛋白酶抑制剂 A3K 显著降低了角膜中的 TNF-α 水平。