Liu Kanghan, Huang Yixiong, Xiao Wuhao, Liao Jin, Ouyang Shaxi, Liang Yumei, Fu Jia
Department of Nephrology and Laboratory of Kidney Disease, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha Clinical Research Center for Kidney Disease, Hunan Clinical Research Center for Chronic Kidney Disease, Changsha, 410002, Hunan, China.
Department of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61, Jiefangxi Road, Changsha, 410002, Hunan, China.
Clin Exp Nephrol. 2025 Jun 17. doi: 10.1007/s10157-025-02707-7.
Resveratrol glycoside (also known as polydatin, PLD), known for its anti-inflammatory and anti-fibrotic properties, has shown potential in mitigating fibrosis in various organs. This study aimed to investigate the effects of PLD on high glucose-induced peritoneal fibrosis and its underlying mechanisms, focusing on the NOD-like receptor protein 3 (NLRP3)/interleukin-1 beta (IL-1β)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling.
Eighteen Sprague-Dawley rats were divided into three groups: control, peritoneal fibrosis, and resveratrol glycoside treatment. Histological and immunohistochemical analyses were performed to assess peritoneal fibrosis. Human peritoneal mesothelial cells (HMrSV5) were treated with high glucose and PLD to evaluate cell morphology, viability, and the expression of fibrosis and inflammatory markers via Western Blot and immunofluorescence.
PLD significantly reduced peritoneal fibrosis in rats, as evidenced by histological analyses showing decreased tissue thickness and collagen deposition. It also downregulated the expression of transforming growth factor beta 1 (TGF-β1), collagen type I (Col I), alpha-smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), NLRP3, phosphorylated p65 subunit of NF-κB (p-p65), IL-1β, interleukin-18 (IL-18), cleaved caspase-1 p20 subunit (caspase-1p20) and ROS level, while upregulating E-cadherin. In HMrSV5 cells, PLD mitigated high glucose-induced epithelial-mesenchymal transition, angiogenesis, reactive oxygen species (ROS) production and inflammation, which was reversed by overexpression of NLRP3, suggesting the involvement of the NLRP3/IL-1β/NF-κB pathway.
PLD alleviates high glucose-induced peritoneal fibrosis, angiogenesis, ROS production and inflammation by inhibiting the NLRP3/IL-1β/NF-κB signaling pathway, highlighting its potential as a therapeutic agent for peritoneal fibrosis.
白藜芦醇苷（又称虎杖苷，PLD）以其抗炎和抗纤维化特性而闻名，已显示出减轻各器官纤维化的潜力。本研究旨在探讨PLD对高糖诱导的腹膜纤维化的影响及其潜在机制，重点关注NOD样受体蛋白3（NLRP3）/白细胞介素-1β（IL-1β）/活化B细胞核因子κB（NF-κB）信号通路。
将18只Sprague-Dawley大鼠分为三组：对照组、腹膜纤维化组和白藜芦醇苷治疗组。进行组织学和免疫组化分析以评估腹膜纤维化。用高糖和PLD处理人腹膜间皮细胞（HMrSV5），通过蛋白质免疫印迹法和免疫荧光法评估细胞形态、活力以及纤维化和炎症标志物的表达。
组织学分析显示组织厚度和胶原沉积减少，证明PLD可显著减轻大鼠腹膜纤维化。它还下调了转化生长因子β1（TGF-β1）、I型胶原（Col I）、α平滑肌肌动蛋白（α-SMA）、血管内皮生长因子（VEGF）、NLRP3、NF-κB的磷酸化p65亚基（p-p65）、IL-1β、白细胞介素-18（IL-18）、半胱天冬酶-1 p20亚基（caspase-1p20）的表达以及ROS水平，同时上调E-钙黏蛋白。在HMrSV5细胞中，PLD减轻了高糖诱导的上皮-间质转化、血管生成、活性氧（ROS）产生和炎症，而NLRP3的过表达可逆转这些作用，提示NLRP3/IL-1β/NF-κB信号通路参与其中。
PLD通过抑制NLRP3/IL-1β/NF-κB信号通路减轻高糖诱导的腹膜纤维化、血管生成、ROS产生和炎症，突出了其作为腹膜纤维化治疗药物的潜力。
