Fu Tianxiao, Lu Wenwen, Wu Danbin, Xu Li, Wu Guolin
Department of Traditional Chinese Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79, Qingchun Road, Shangcheng District, Hangzhou City, 310000, Zhejiang Province, China.
Int Ophthalmol. 2025 Jun 5;45(1):230. doi: 10.1007/s10792-025-03607-1.
Sjögren's syndrome-related dry eye disease (SS-DED) is an autoimmune disorder characterized by ocular surface inflammation and lacrimal gland dysfunction, with limited clinical treatment options currently available.
Based on the traditional Chinese medicine theory of "the liver opens into the eyes" and the modern "gut-eye axis" hypothesis. This study investigated the therapeutic effects and immunomodulatory mechanisms of total glucosides of paeony (TGP) using a NOD mouse model.
The results showed that TGP significantly increased tear secretion in SS mice, alleviated corneal and conjunctival damage, improved pathological changes in the Harderian gland, reduced inflammatory infiltration, and restored glandular secretory function. At the molecular level, TGP markedly downregulated pro-inflammatory cytokines such as IL-6 and IL-17 while upregulating anti-inflammatory factors like IL-10 and TGF-β, effectively modulating the Th17/Treg immune balance. Additionally, TGP enhanced the expression of tight junction proteins (ZO-1, Occludin, and Claudin-3) in SS mice, repairing intestinal barrier function. 16S rRNA sequencing analysis revealed that TGP intervention regulated gut microbiota composition in SS mice, reducing the Firmicutes/Bacteroidetes ratio and increasing the abundance of beneficial bacteria such as Lactobacillus. Functional prediction analysis indicated that TGP-modulated gut microbiota primarily participated in key metabolic pathways, including carbohydrate and amino acid metabolism.
In conclusion, TGP can ameliorate ocular surface damage in SS mice by regulating gut microecology and immune homeostasis via the "gut-eye axis" pathway. Our study not only provides a novel therapeutic strategy for SS-DED but also offers scientific evidence for the modernization of traditional Chinese medicine theories.
干燥综合征相关干眼疾病（SS-DED）是一种自身免疫性疾病，其特征为眼表炎症和泪腺功能障碍，目前临床治疗选择有限。
基于中医“肝开窍于目”理论和现代“肠-眼轴”假说。本研究使用非肥胖糖尿病（NOD）小鼠模型探究了白芍总苷（TGP）的治疗效果及免疫调节机制。
结果显示，TGP显著增加了SS小鼠的泪液分泌，减轻了角膜和结膜损伤，改善了哈德氏腺的病理变化，减少了炎症浸润，并恢复了腺体分泌功能。在分子水平上，TGP显著下调促炎细胞因子如IL-6和IL-17，同时上调抗炎因子如IL-10和TGF-β，有效调节Th17/Treg免疫平衡。此外，TGP增强了SS小鼠紧密连接蛋白（ZO-1、闭合蛋白和Claudin-3）的表达，修复了肠道屏障功能。16S rRNA测序分析显示，TGP干预调节了SS小鼠的肠道微生物群组成，降低了厚壁菌门/拟杆菌门的比例，并增加了有益菌如乳酸杆菌的丰度。功能预测分析表明，TGP调节的肠道微生物群主要参与关键代谢途径，包括碳水化合物和氨基酸代谢。
总之，TGP可通过“肠-眼轴”途径调节肠道微生态和免疫稳态，改善SS小鼠的眼表损伤。我们的研究不仅为SS-DED提供了一种新的治疗策略，也为中医理论现代化提供了科学依据。
