Abstract：
Studies have found that the intake of environmental endocrine disruptors was positively correlated with the occurrence of gastric diseases. The aim of this study was to determine whether nonylphenol (NP) exposure can induce gastric inflammation and whether its mechanism was related to NF-κB/NLRP3 signaling pathway. In vivo, male SD rats were randomly divided into 4 groups (12 rats/group): control group (corn oil), NP low (0.4 mg/kg), medium (4 mg/kg), and high (40 mg/kg) dose groups. After 33 weeks of NP chronic exposure, it was found pathological changes in gastric tissues, increase the release of inflammatory factors, and effects expressions of genes related to the NF-κB/NLRP3 signaling pathway. In vitro, the GES-1 cell experiments, which included four groups: control (0 µmol/L NP), L (2.5 µmol/L NP), M (40 µmol/L NP), and H (60 µmol/L NP), confirmed that NP increased the release of inflammatory factors in the cells, and up-regulated the expression of proteins related to NF-κB/NLRP3 signaling pathway. Furthermore, when pyrrolidinedithiocarbamate ammonium (PDTC) blocked the NF-κB signaling pathway, it was found that the expression of related proteins in the NF-κB/NLRP3 signaling pathway was decreased, and the release of inflammatory factors in GES-1 cells caused by NP was also attenuated. The results of this study indicated that NP can induce inflammation in the stomach in vivo and in vitro, and its mechanism was related to the NF-κB/NLRP3 signaling pathway. These findings provided a new perspective on the mechanism of inflammatory response induced by exposure to environmental endocrine disruptors. Also, these findings indicated that therapeutic strategies for the NF-κB/NLRP3 signaling pathway may be new methods to treat inflammatory diseases.
摘要：
研究发现环境内分泌干扰物的摄入与胃病的发生呈正相关。本研究的目的是确定壬基酚（NP）暴露是否会引起胃部炎症，其机制是否与NF-κB/NLRP3信号通路有关。在体内,雄性SD大鼠随机分为4组(12只/组):对照组(玉米油),NP低（0.4mg/kg），培养基（4mg/kg），和高（40mg/kg）剂量组。NP慢性暴露33周后，发现胃组织有病理变化，增加炎症因子的释放，并影响NF-κB/NLRP3信号通路相关基因的表达。体外，GES-1细胞实验，其中包括四组：对照组（0μmol/LNP），L(2.5μmol/LNP),M（40μmol/LNP），和H（60μmol/LNP），证实NP增加了细胞中炎症因子的释放，并上调NF-κB/NLRP3信号通路相关蛋白的表达。此外，当吡咯烷二硫代氨基甲酸铵（PDTC）阻断NF-κB信号通路时，结果发现NF-κB/NLRP3信号通路中相关蛋白的表达降低,NP引起的GES-1细胞炎症因子的释放也减弱。这项研究的结果表明，NP可以在体内和体外诱导胃部炎症，其机制与NF-κB/NLRP3信号通路有关。这些发现为暴露于环境内分泌干扰物引起的炎症反应的机制提供了新的视角。此外，这些发现表明NF-κB/NLRP3信号通路的治疗策略可能是治疗炎症性疾病的新方法。
