目的 探讨精神应激诱发十二指肠炎症的作用及相关分子机制。 方法 本研究构建了慢性束缚应激（CRS）小鼠模型，并结合体外培养的单核/巨噬细胞模型（RAW264.7和THP-1），采用RT-qPCR、Western blot、HE染色和免疫组化等技术，检测了炎症因子、焦亡通路相关蛋白以及激素受体的表达变化。 结果 CRS能够显著诱发小鼠十二指肠组织的炎症反应，表现为IL-1β、IL-18和TNF-α等炎症因子水平及组织学评分的升高（P < 0.05）。该促炎效应由β2肾上腺素能受体（β2AR）介导，而非糖皮质激素受体。进一步研究发现，CRS促进了十二指肠黏膜巨噬细胞的增生，而通过化学方法清除巨噬细胞则能有效抑制CRS诱导的炎症反应（P < 0.01）。机制上，CRS激活了十二指肠组织中巨噬细胞的NLRP3/Caspase1/GSDMD介导的经典焦亡通路，表现为GSDMD-N端活化片段的蛋白水平升高。体外实验证实，应激激素肾上腺素能直接通过β2AR激活巨噬细胞的焦亡通路，促进炎症因子释放（P < 0.05）。 结论 精神应激通过激活交感-肾上腺髓质系统，经由β2AR信号通路促进十二指肠巨噬细胞发生GSDMD介导的焦亡，最终导致十二指肠黏膜炎症。

Objective To investigate whether psychological stress causes duodenal inflammation and the related molecular mechanisms. Methods This study employed a chronic restraint stress （CRS） mouse model， which was supplemented with in vitro models using RAW264.7 and THP-1 monocytic/macrophage cell lines. Techniques including RT-qPCR， Western blot， HE staining， and immunohistochemistry were used to investigate the expression alterations of inflammatory cytokines， pyroptosis pathway-related proteins， and hormone receptors. Results CRS significantly triggered an inflammatory response in the duodenal tissue of mice， which was characterized by heightened levels of inflammatory cytokines such as IL-1β， IL-18， and TNF-α， along with elevated histological scores （P < 0.05）. This pro-inflammatory effect was mediated by the β2-adrenergic receptor （β2AR）， rather than the glucocorticoid receptor. Further research demonstrated that CRS facilitated the proliferation of macrophages in the duodenal mucosa， and the chemical depletion of macrophages effectively inhibited CRS-induced inflammation （P < 0.01）. Mechanistically， CRS activated the classical NLRP3/Caspase1/GSDMD-mediated pyroptosis pathway in duodenal macrophages， as indicated by the increased protein level of the activated N-terminal fragment of GSDMD. In vitro experiments verified that the stress hormone epinephrine could directly activate the macrophage pyroptosis pathway and stimulate the release of inflammatory cytokines via β2AR （P < 0.05）. Conclusions Psychological stress triggers the activation of the sympathetic-adrenal medulla system. This activation promotes GSDMD-mediated pyroptosis in duodenal macrophages through the β2AR signaling pathway， ultimately resulting in duodenal mucosal inflammation.