背景:近年来,胰岛素滴眼液越来越受到研究者和眼科医生的关注。这项研究的目的是研究胰岛素滴眼液在患有角膜伤口的糖尿病小鼠中的功效和可能的作用机制。
方法:建立1型糖尿病模型,建立2.5mm角膜上皮损伤模型。我们用角膜荧光素染色,苏木精-伊红(H-E)染色和Cochet-Bonnet美度计检查伤口愈合过程。随后,Ki-67,IL-1β的表达水平,β3-微管蛋白和神经肽,包括P物质(SP)和降钙素基因相关肽(CGRP),在角膜损伤后72小时进行检查。
结果:荧光素染色显示,与生理盐水治疗相比,糖尿病小鼠角膜上皮损伤的恢复加速,Ki-67的过表达进一步证明了这一点。此外,72h的胰岛素应用减弱了炎性细胞因子的表达和中性粒细胞的浸润。值得注意的是,结果表明,局部胰岛素治疗增加了角膜上皮神经的密度,以及神经肽SP和CGRP释放,在愈合的角膜中通过免疫荧光染色。
结论:我们的结果表明,胰岛素滴眼液可能通过促进神经再生和增加神经肽SP和CGRP水平来加速糖尿病小鼠角膜伤口的愈合和减轻炎症反应。
BACKGROUND: In recent years, insulin eye drops have attracted increasing attention from researchers and ophthalmologists. The aim of this study was to investigate the efficacy and possible mechanism of action of insulin eye drops in diabetic mice with corneal wounds.
METHODS: A type 1 diabetes model was induced, and a corneal epithelial injury model of 2.5 mm was established. We used corneal fluorescein staining, hematoxylin-eosin (H-E) staining and the Cochet-Bonnet esthesiometer to examine the process of wound healing. Subsequently, the expression levels of Ki-67, IL-1β, β3-tubulin and neuropeptides, including substance P (SP) and calcitonin gene-related peptide (CGRP), were examined at 72 h after corneal injury.
RESULTS: Fluorescein staining demonstrated an acceleration of the recovery of corneal epithelial injury in diabetic mice compared with the saline treatment, which was further evidenced by the overexpression of Ki-67. Moreover, 72 h of insulin application attenuated the expression of inflammatory cytokines and neutrophil infiltration. Remarkably, the results demonstrated that topical insulin treatment enhanced the density of corneal epithelial nerves, as well as neuropeptide SP and CGRP release, in the healing cornea via immunofluorescence staining.
CONCLUSIONS: Our results indicated that insulin eye drops may accelerate corneal wound healing and decrease inflammatory responses in diabetic mice by promoting nerve regeneration and increasing levels of neuropeptides SP and CGRP.