蜗牛粘液中肝素样糖胺聚糖在小鼠干眼模型中的有效性
Effectiveness of a heparin-like glycosaminoglycan from snail mucus in a murine model of dry eye.
摘要(中文译文)
干眼病（DED）是一种多因素眼表疾病，以泪膜不稳定、炎症和上皮损伤为特征，导致不适和视觉障碍。目前的治疗在疗效和安全性方面仍然有限。从非洲大蜗牛（Achatina fulica）黏液中所纯化的一种类肝素糖胺聚糖（AFG）具有潜在的再生和抗炎特性。本研究旨在评估AFG对干眼病的治疗效果及其机制。通过细胞活力、增殖、迁移以及增殖相关和黏蛋白相关基因的qRT-PCR分析，评估了AFG对人角膜上皮（HCE）细胞的影响。在体内实验中，采用苯扎氯铵（BAC）诱导的小鼠干眼病模型，评估局部AFG治疗后的角膜完整性、泪液分泌、组织学变化、炎症浸润及分子表达。使用qRT-PCR、蛋白质印迹和免疫荧光检测基因和蛋白表达水平。AFG对HCE细胞无细胞毒性，并通过上调K14、KI67、MUC1和MUC4显著增强其增殖和迁移。在干眼病小鼠模型中，局部AFG治疗明显改善角膜完整性、增加泪液分泌并恢复上皮结构。AFG上调上皮分化和修复标志物（K12、K14、PAX6）的表达，同时下调炎症基因（IL-1β、TNF-α、IL-6、MMP-9、CD45）并减少巨噬细胞浸润。这些效应共同促进了角膜上皮再生和泪膜稳定。AFG通过增强角膜上皮增殖、促进黏蛋白分泌和抑制炎症来缓解干眼病。其类肝素糖胺聚糖结构赋予其生物相容性和多功能活性，凸显AFG作为角膜修复和干眼管理局部治疗的有前景候选药物。
Abstract
Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability, inflammation, and epithelial injury, leading to discomfort and visual disturbance. Current treatments remain limited in efficacy and safety. A heparin-like glycosaminoglycan purified from the snail mucus of Achatina fulica (AFG) exhibits potential regenerative and anti-inflammatory properties. This study aimed to evaluate the therapeutic effectiveness and mechanism of AFG in DED. The effects of AFG on human corneal epithelial (HCE) cells were assessed by cell viability, proliferation, migration, and qRT-PCR analyses of proliferation- and mucin-related genes. In vivo, a benzalkonium chloride (BAC)-induced murine model of DED was used to evaluate corneal integrity, tear production, histological changes, inflammatory infiltration, and molecular expression following topical AFG treatment. Gene and protein expression levels were examined using qRT-PCR, western blotting, and immunofluorescence. AFG showed no cytotoxicity toward HCE cells and significantly enhanced their proliferation and migration by upregulating K14, KI67, MUC1, and MUC4. In the DED mouse model, topical AFG treatment markedly improved corneal integrity, increased tear secretion, and restored epithelial structure. AFG upregulated the expression of epithelial differentiation and repair markers (K12, K14, PAX6) while downregulating inflammatory genes (IL-1β, TNF-α, IL-6, MMP-9, CD45) and reducing macrophage infiltration. These effects collectively promoted corneal epithelial regeneration and tear film stabilization. AFG alleviates dry eye disease by enhancing corneal epithelial proliferation, promoting mucin secretion, and suppressing inflammation. Its heparin-like glycosaminoglycan structure enables biocompatible and multifunctional activity, highlighting AFG as a promising candidate for topical therapy in corneal repair and dry eye management.
如何引用
AMA
Shangkun Ou, Lingli Zhang, Lisha Lin, Liying Zhang, Hao Jiang, Qiurong Long, et al. Effectiveness of a heparin-like glycosaminoglycan from snail mucus in a murine model of dry eye.. Journal of translational medicine. 2026; doi:10.1186/s12967-026-08609-w.
APA
Shangkun Ou, Lingli Zhang, Lisha Lin, Liying Zhang, Hao Jiang, Qiurong Long, et al (2026). Effectiveness of a heparin-like glycosaminoglycan from snail mucus in a murine model of dry eye.. Journal of translational medicine. https://doi.org/10.1186/s12967-026-08609-w
GB/T 7714
Shangkun Ou, Lingli Zhang, Lisha Lin, Liying Zhang, Hao Jiang, Qiurong Long, et al. Effectiveness of a heparin-like glycosaminoglycan from snail mucus in a murine model of dry eye.[J]. Journal of translational medicine, 2026 doi:10.1186/s12967-026-08609-w.
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