Sodium tanshinone IIA sulfonate attenuates sepsis-associated brain injury via inhibiting NOD-like receptor 3/caspase-1/gasdermin D-mediated pyroptosis

作者：Yaqin Song, Wei-Ji Lin, Hongjie Hu, Shuhui Wu, Jing Liang, Qing Lü, Wei Zhu · 发表于：International Immunopharmacology · 年份：2023 · DOI：10.1016/j.intimp.2023.110111 · 被引用次数：21 · 研究领域：Inflammasome and immune disorders、Inflammation biomarkers and pathways、Neuroinflammation and Neurodegeneration Mechanisms

BACKGROUND: Sodium tanshinone IIA sulfonate (STS) has been reported to protect organ function in sepsis. However, the attenuation of sepsis-associated brain injury and its underlying mechanisms by STS has not been established. METHODS: C57BL/6 mice were used to establish the cecal ligation perforation (CLP) model, and STS was injected intraperitoneally 30 min before the surgery. The BV2 cells were stimulated by lipopolysaccharide after being pre-treated with STS for 4 h. The STS protective effects against brain injury and in vivo anti-neuroinflammatory effects were investigated using the 48-hour survival rate and body weight changes, brain water content, histopathological staining, immunohistochemistry, ELISA, RT-qPCR, and transmission electron microscopy. The pro-inflammatory cytokines of BV2 cells were detected by ELISA and RT-qPCR. At last, the levels of NOD-like receptor 3 (NLRP3) inflammasome activation and pyroptosis in brain tissues of the CLP model and BV2 cells were detected using western blotting. RESULTS: STS increased the survival rate, decreased brain water content, and improved brain pathological damage in the CLP models. STS increased the expressions of tight junction proteins ZO-1 and Claudin5 while reducing the expressions of tumor necrosis factor α (TNF-α), interleukin-1β(IL-1β), and interleukin-18 (IL-18) in the brain tissues of the CLP models. Meanwhile, STS inhibited microglial activation and M1-type polarization in vitro and in vivo. The NLRP3/caspase-1/...