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D-β-羟基丁酸可预防使用跑步机的大鼠干眼模型中的角膜上皮疾病。

D-beta-hydroxybutyrate protects against corneal epithelial disorders in a rat dry eye model with jogging board.

作者信息

Nakamura Shigeru, Shibuya Michiko, Nakashima Hideo, Imagawa Tomohiro, Uehara Masato, Tsubota Kazuo

机构信息

Ophtecs Corporation, Hyogo, Japan.

出版信息

Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2379-87. doi: 10.1167/iovs.04-1344.

Abstract

PURPOSE

The purpose of this study was to establish a rat dry eye model of corneal epithelial disorders by inducing improper tear dynamics and change in blink frequency. The protective effect of d-beta-hydroxybutyrate (HBA) on the corneal epithelia was also investigated.

METHODS

A series of treatments were performed under continuous exposure to low-humidity airflow. Rats were placed on a jogging board (JB) made of a plastic pipe for 7.5 h/d, and, for 16.5 hours, they were placed in individual cages without JB treatment. The resultant changes in tear dynamics and corneal epithelial structure were then analyzed. Five days after the rats were exposed to the treatment, eyes that showed corneal fluorescein staining were examined, to investigate the effect of HBA, by administration of eye drops containing 80 mM HBA four times daily during JB treatment for 5 days.

RESULTS

Significant reductions in blink frequency, Schirmer score, and tear clearance were recorded during JB treatment in eyes that showed persistent punctate staining of almost one half of the corneal surface. The application of HBA-containing eye drops significantly reduced the punctate staining compared with the initial or phosphate-buffered saline-treated eyes.

CONCLUSIONS

This rat dry eye model, established by repeated JB treatment in desiccating conditions, induced abnormal tear dynamics and superficial punctate keratopathy similar to that in humans. These findings suggest the potential clinical application of HBA in corneal surface epithelial disorders in patients with moderate to mild dry eye.

摘要

目的

本研究的目的是通过诱导泪液动力学异常和眨眼频率改变,建立一种角膜上皮疾病的大鼠干眼模型。同时还研究了d-β-羟基丁酸(HBA)对角膜上皮的保护作用。

方法

在持续暴露于低湿度气流的条件下进行一系列处理。将大鼠置于由塑料管制成的慢跑板(JB)上,每天7.5小时,其余16.5小时置于单独的笼子中,不进行JB处理。然后分析由此产生的泪液动力学和角膜上皮结构的变化。在大鼠接受处理5天后,检查出现角膜荧光素染色的眼睛,通过在JB处理的5天内每天4次滴注含80 mM HBA的眼药水来研究HBA的作用。

结果

在JB处理期间,角膜表面几乎一半出现持续性点状染色的眼睛,其眨眼频率、泪液分泌试验评分和泪液清除率均显著降低。与初始或磷酸盐缓冲盐水处理的眼睛相比,滴注含HBA的眼药水可显著减少点状染色。

结论

通过在干燥条件下重复进行JB处理建立的这种大鼠干眼模型,可诱导出与人类相似的异常泪液动力学和浅层点状角膜病变。这些发现提示HBA在中轻度干眼患者角膜表面上皮疾病中具有潜在的临床应用价值。

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