Lychee seed polyphenol protects blood–retinal barrier by increasing tight joint proteins and inhibiting the activation of TLR4/MYD88/NF-κB-mediated NLRP3 inflammasome

Emerging evidence indicates that blood–retinal barrier (BRB) damage is the main cause of diabetic retinopathy (DR), and the downregulation of tight proteins (TJs) located between endothelial cells and the activation of NLRP3 inflammasome-mediated inflammation in Müller cells result in BRB injury. In this study, we aimed to study the protective effect of lychee seed polyphenol (LSP) on BRB integrity and the mechanism of action. By establishing a cellular model of BRB injury by using high glucose (HG)-induced hRECs or co-culture system of hRECs with MIO-M1 cells, we found that LSP significantly maintained the integrity of monolayer of hRECs as revealed by the decreased PD40 permeability and increased TJs, including ZO-1, Occludin, and Claudin 5. In addition, LSP inhibited the NLRP3 inflammasome activation and the levels of inflammatory cytokines via the TLR4/MYD88/NF-κB pathway. Collectively, this study provides valuable insight into the utilization of LSP in the treatment of DR.

越来越多的证据表明，血视网膜屏障（blood–retinal barrier, BRB）损伤是糖尿病视网膜病变（diabetic retinopathy, DR）的主要致病原因；内皮细胞间紧密连接蛋白（tight proteins, TJs）表达下调，以及米勒细胞中NLRP3炎症小体介导的炎症活化，均可引发血视网膜屏障损伤。本研究旨在探讨荔枝籽多酚（lychee seed polyphenol, LSP）对血视网膜屏障完整性的保护作用及其作用机制。本研究通过高糖（high glucose, HG）诱导的人视网膜内皮细胞（hRECs），或hRECs与MIO-M1细胞共培养体系构建血视网膜屏障损伤细胞模型，实验结果显示，荔枝籽多酚可显著维持人视网膜内皮细胞单层的完整性：具体表现为PD40通透性降低，以及ZO-1、闭合蛋白（Occludin）、Claudin-5等紧密连接蛋白的表达水平显著升高。此外，荔枝籽多酚可通过TLR4/MYD88/NF-κB信号通路抑制NLRP3炎症小体活化，并下调炎症细胞因子的表达水平。综上，本研究为荔枝籽多酚在糖尿病视网膜病变治疗中的应用提供了具有重要价值的理论依据。