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基于TLR4/NLRP3信号通路及其对中性粒细胞胞外陷阱形成的影响探讨人参皂苷Rg对急性痛风性关节炎的作用机制

Based on the TLR4/NLRP3 Pathway and Its Impact on the Formation of NETs to Explore the Mechanism of Ginsenoside Rg on Acute Gouty Arthritis.

作者信息

Li Zhiman, Yu Yang, Sun Qiang, Li Zhilong, Huo Xiaohui, Sha Jiyue, Qu Di, Sun Yinshi

机构信息

Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China.

College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.

出版信息

Int J Mol Sci. 2025 Apr 29;26(9):4233. doi: 10.3390/ijms26094233.

DOI:10.3390/ijms26094233
PMID:40362468
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12071870/
Abstract

This study investigated whether ginsenoside Rg (G-Rg) alleviated acute gouty arthritis (AGA) in rats by modulating the TLR4/NLRP3 pathway and neutrophil extracellular trap (NET) formation. Rats were orally administered G-Rg or colchicine (Col) for 7 days, and monosodium urate (MSU) was injected into the ankle joints on day 5 to induce AGA. Joint swelling, histopathology (HE staining), and serum markers (MPO, NE, MPO-DNA, IL-6, IL-1β; ELISA) were assessed at the baseline and 6-36 h post-modeling. Western blot and immunofluorescence analyzed the NET-related and TLR4/NLRP3 pathway proteins in synovial tissue. G-Rg significantly reduced ankle swelling and synovial inflammation compared with the AGA group, lowered the serum IL-6, IL-1β, MPO, NE, and MPO-DNA levels, and suppressed NET-associated protein expression. Mechanistically, G-Rg downregulated TLR4/NLRP3 pathway activation in synovial tissue. These findings suggest that G-Rg mitigates AGA by inhibiting TLR4/NLRP3 signaling, thereby reducing inflammatory cytokine release and NET formation.

摘要

本研究调查了人参皂苷Rg(G-Rg)是否通过调节TLR4/NLRP3信号通路和中性粒细胞胞外陷阱(NET)形成来减轻大鼠急性痛风性关节炎(AGA)。大鼠口服G-Rg或秋水仙碱(Col)7天,并在第5天向踝关节注射尿酸钠(MSU)以诱导AGA。在基线以及建模后6 - 36小时评估关节肿胀、组织病理学(苏木精-伊红染色)和血清标志物(MPO、NE、MPO-DNA、IL-6、IL-1β;酶联免疫吸附测定)。蛋白质免疫印迹法和免疫荧光法分析滑膜组织中与NET相关的蛋白以及TLR4/NLRP3信号通路蛋白。与AGA组相比,G-Rg显著减轻了踝关节肿胀和滑膜炎症,降低了血清IL-6、IL-1β、MPO、NE和MPO-DNA水平,并抑制了与NET相关的蛋白表达。机制上,G-Rg下调了滑膜组织中TLR4/NLRP3信号通路的激活。这些发现表明,G-Rg通过抑制TLR4/NLRP3信号传导减轻AGA,从而减少炎性细胞因子释放和NET形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e08/12071870/1b393e5ac0db/ijms-26-04233-g006.jpg
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