Machida Hospital, Kochi City, Kochi, Japan.
Br J Ophthalmol. 2013 Jul;97(7):912-6. doi: 10.1136/bjophthalmol-2012-302868. Epub 2013 Apr 20.
Disruption of corneal epithelial barrier function by inflammation may contribute to the development of dry eye. The effects of rebamipide, a drug used for the treatment of dry eye, on barrier function and cytokine expression in a human corneal epithelial (HCE) cell line were examined.
Barrier function of HCE cells was evaluated by measurement of transepithelial electrical resistance (TER). The subcellular localisation of the tight junction protein zonula occludens (ZO)-1 was examined by immunofluorescence analysis. The release of cytokines was determined with ELISAs, and the intracellular abundance of cytokine mRNAs was quantitated by reverse transcription and real-time PCR analysis. Degradation of the nuclear factor-κB inhibitor IκBα was detected by immunoblot analysis.
Rebamipide increased TER of HCE cells in a concentration-dependent manner as well as attenuating the loss of TER and the disappearance of ZO-1 from the cell surface induced by tumour necrosis factor α (TNFα). Rebamipide also suppressed TNFα-induced expression of interleukin-6 and interleukin-8 at the mRNA and protein levels and inhibited the TNFα-induced degradation of IκBα.
The upregulation of barrier function and the anti-inflammatory effects of rebamipide, together with its mucin secretagogue activity, may contribute to the effectiveness of this drug for the treatment of dry eye.
炎症会破坏角膜上皮屏障功能，可能导致干眼的发生。本研究旨在观察瑞巴派特（一种用于治疗干眼的药物）对人角膜上皮（HCE）细胞系屏障功能和细胞因子表达的影响。
通过测量跨上皮电阻（TER）评估 HCE 细胞的屏障功能。通过免疫荧光分析检测紧密连接蛋白闭合蛋白（ZO）-1的亚细胞定位。通过 ELISA 测定细胞因子的释放量，并通过反转录和实时 PCR 分析定量细胞内细胞因子 mRNA 的丰度。通过免疫印迹分析检测核因子-κB 抑制剂 IκBα的降解。
瑞巴派特呈浓度依赖性增加 HCE 细胞的 TER，并减轻 TNFα诱导的 TER 丧失和 ZO-1 从细胞表面消失。瑞巴派特还抑制 TNFα诱导的白细胞介素-6 和白细胞介素-8 的 mRNA 和蛋白表达，并抑制 TNFα诱导的 IκBα降解。
瑞巴派特对屏障功能的上调作用和抗炎作用，以及其黏液分泌作用，可能有助于该药治疗干眼的有效性。
