Clinical Psychology, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Guangxi Key Laboratory of Reproductive Health and Birth Defect Prevention, Nanning, China.
Department of Emergency, The People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical Sciences, Nanning 530021, China.
Ecotoxicol Environ Saf. 2024 Oct 1;284:116912. doi: 10.1016/j.ecoenv.2024.116912. Epub 2024 Aug 23.
Long-term consumption of swainsonine could be poisonous to livestock, including facilitating apoptosis by impairing lysosomal function and inhibiting autophagic degradation, leading to liver inflammation and even death in livestock. However, the mechanism by swainsonine induced systemic inflammatory responses remained unclear, especially the effects of swainsonine on intestinal permeability, lipopolysaccharide (LPS) level and oxidative stress response were unknown. In this study, swainsonine increased intestinal permeability as evidenced by the significant down-regulation of colonic goblet cells, Akkermansia muciniphila and intestinal tight junction protein Occludin, Claudin 1 and ZO-1, and the significant up-regulation of mRNA expression level of the intestinal permeability indicator protein tyrosine phosphatase receptor type H (Ptprh) in the ileum of mice. Simultaneously, the elevated LPS biosynthetic genes in intestinal microbiota and increased intestinal permeability facilitated more bacterial endotoxin LPS to enter the blood. High concentration of free-form LPS induced high levels of proinflammatory cytokines and oxidative stress response, thereby causing the systemic inflammation. These findings provided a new perspective on swainsonine-induced systemic inflammation, suggesting that intestinal permeability and free-form LPS level may be the potential trigger factors.
长期食用苦马豆素可能对牲畜有毒，包括通过损害溶酶体功能和抑制自噬降解来促进细胞凋亡，从而导致牲畜肝脏炎症甚至死亡。然而，苦马豆素诱导全身炎症反应的机制尚不清楚，特别是苦马豆素对肠道通透性、脂多糖（LPS）水平和氧化应激反应的影响尚不清楚。在这项研究中，苦马豆素增加了肠道通透性，这表现在结肠杯状细胞、阿克曼氏菌粘液菌和肠道紧密连接蛋白 Occludin、Claudin 1 和 ZO-1 的显著下调，以及回肠中肠道通透性标志物蛋白酪氨酸磷酸酶受体 H（Ptprh）的 mRNA 表达水平的显著上调。同时，肠道微生物群中 LPS 生物合成基因的升高和肠道通透性的增加促进了更多的细菌内毒素 LPS 进入血液。游离形式 LPS 的高浓度诱导高水平的促炎细胞因子和氧化应激反应，从而导致全身炎症。这些发现为苦马豆素诱导的全身炎症提供了一个新的视角，表明肠道通透性和游离形式 LPS 水平可能是潜在的触发因素。
