Sepsis is a clinical syndrome triggered by an imbalanced host response to pathogens that can lead to multiple organ dysfunction. The immune response and barrier function of the gut play an important role in the pathogenesis and progression of sepsis. This study aimed to explore the potential role of natural alkaloid Liensinine in the treatment of intestinal injury caused by sepsis and its possible molecular mechanism. In this study, a mouse model of sepsis was established by injecting LPS to explore the protective effect of Liensinine on intestinal injury in sepsis. The results showed that Liensinine could reduce the intestinal damage caused by LPS and increase the number of goblet cells. Furthermore, it decreased the release of inflammatory cytokines by inhibiting NF-kB phosphorylation and NLRP3 inflammasome synthesis. Liensinine also reduced the oxidative stress and ROS accumulation caused by LPS, and played an anti-oxidative stress role by regulating the Nrf2/keap1 signaling pathway. In addition, Liensinine alleviated the inhibition of intestinal autophagy caused by LPS by inhibiting the PI3K/Akt/mTOR pathway. And then it reduced the excessive apoptosis of intestinal cells. This study provides valuable insights for sepsis prevention and treatment, offering a potential therapeutic candidate to protect against intestinal injury and regulate the inflammatory response in sepsis.

脓毒症是一种由宿主对病原体反应失衡引发的临床综合征，可导致多器官功能障碍。肠道的免疫反应和屏障功能在脓毒症的发病机制和进展中发挥着重要作用。本研究旨在探讨天然生物碱莲心碱治疗脓毒症引起的肠道损伤的潜在作用及其可能的分子机制。本研究通过注射LPS建立脓毒症小鼠模型，探讨莲心碱对脓毒症肠道损伤的保护作用。结果表明，莲心碱可以减轻LPS引起的肠道损伤，增加杯状细胞的数量。此外，它还通过抑制 NF-kB 磷酸化和 NLRP3 炎症小体合成来减少炎症细胞因子的释放。莲心碱还能减少LPS引起的氧化应激和ROS积累，通过调节Nrf2/keap1信号通路发挥抗氧化应激作用。此外，莲心碱通过抑制PI3K/Akt/mTOR通路，减轻LPS引起的肠道自噬抑制。进而减少肠道细胞的过度凋亡。这项研究为脓毒症的预防和治疗提供了宝贵的见解，为预防肠道损伤和调节脓毒症中的炎症反应提供了潜在的治疗候选者。