Hydrogen sulfide (H₂S) has been reported to participate in intestinal mucosal defense and repair. However, the precise regulatory mechanisms of H₂S in ulcerative colitis (UC) remain unclear. We explored the effects of sodium hydrosulfide (NaHS), a donor of H₂S, in dextran sulfate sodium (DSS)-induced colitis in rats. The pathologic features were determined by analyzing the hematoxylin and eosin-stained samples. Interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and myeloperoxidase (MPO) levels were determined using ELISA. The presence of cystathionine-γ-lyase (CSE) and light chain 3B (LC3B) were determined using immunohistochemical and immunofluorescence (IF) approaches, respectively. Next, we investigated the effects of NaHS in lipopolysaccharide (LPS)-stimulated human colonic smooth muscle cells (H2940). The level of reactive oxygen species (ROS) was determined using IF. NOD-like receptor 3 (NLRP3) and CSE were detected using western blot and quantitative real-time polymerase chain reaction. Autophagy was determined using western blot, IF, and electron microscopy. NaHS treatment considerably diminished colitis-induced histological injury and proinflammatory cytokine expressions. MPO, CSE, and H₂S were downregulated, whereas LC3B was upregulated after NaHS administration in colitic rats. NaHS remarkably attenuated the levels of ROS, CSE, and NLRP3 in LPS-stimulated cells and enhanced autophagy, as was revealed by increased LC3-II-to-LC3-I ratio, elevated LC3, and decreased p62. Importantly, NaHS promoted autophagosome formation in LPS-treated cells. Exogenous H₂S ameliorates intestinal injury by downregulating inflammation and activation of autophagy, suggesting the potential of NaHS as a therapeutic agent for UC.

中文翻译：

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外源性硫化氢通过抑制 NLRP3 和激活自噬保护溃疡性结肠炎中的结肠细胞

据报道，硫化氢 (H ₂ S) 参与肠粘膜防御和修复。然而，H ₂ S 在溃疡性结肠炎 (UC) 中的精确调节机制仍不清楚。我们探索了氢硫化钠 (NaHS)（H ₂供体）的作用S，在葡聚糖硫酸钠 (DSS) 诱导的大鼠结肠炎中。通过分析苏木精和伊红染色的样品来确定病理特征。使用 ELISA 测定白细胞介素-1β (IL-1β)、IL-6、肿瘤坏死因子-α (TNF-α) 和髓过氧化物酶 (MPO) 水平。分别使用免疫组织化学和免疫荧光 (IF) 方法确定胱硫醚-γ-裂解酶 (CSE) 和轻链 3B (LC3B) 的存在。接下来，我们研究了 NaHS 在脂多糖 (LPS) 刺激的人结肠平滑肌细胞 (H2940) 中的作用。使用 IF 确定活性氧 (ROS) 的水平。NOD样受体3（NLRP3) 和 CSE 使用蛋白质印迹和定量实时聚合酶链反应检测。使用蛋白质印迹、IF 和电子显微镜确定自噬。NaHS 治疗大大减少了结肠炎诱导的组织学损伤和促炎细胞因子的表达。MPO、CSE 和 H ₂ S 被下调，而 LC3B 在结肠炎大鼠中使用 NaHS 后被上调。NaHS 显着降低LPS 刺激细胞中 ROS、CSE 和NLRP3的水平并增强自噬，如 LC3-II 与 LC3-I 比率增加、LC3 升高和 p62 降低所揭示的。重要的是，NaHS 促进了 LPS 处理细胞中自噬体的形成。外源性H ₂S 通过下调炎症和激活自噬来改善肠道损伤，表明 NaHS 作为 UC 治疗剂的潜力。