摘要
目的:探讨牛蒡子苷元对炎症性肠病(IBD)的治疗作用及其作用机制。方法:通过脂多糖(LPS)刺激人肠道细胞Caco-2和葡聚糖硫酸钠(DSS)诱导小鼠在体外和体内建立IBD模型。将24只C57BL/6小鼠随机分为4组:空白对照组(Control)、模型组(Model)、牛蒡子苷元低剂量组(10 mg/kg牛蒡子苷元)和高剂量治疗组(40 mg/kg牛蒡子苷元)。采用ELISA检测Caco-2细胞、小鼠结肠组织炎症因子TNF-α、IL-1β和IL-6、氧化和抗氧化应激标志物MDA、SOD水平。通过Western blot检测Caco-2细胞和小鼠结肠组织中NF-κB p65蛋白磷酸化水平和ZO-1表达。给药第9天处死小鼠,通过HE染色研究结肠组织的组织病理学。结果:体外实验显示牛蒡子苷元显著抑制LPS诱导的炎症因子释放,降低氧化应激水平。Western blot结果显示,牛蒡子苷元降低了NF-κB p65蛋白的磷酸化水平和ZO-1蛋白表达。体内实验显示:与模型组比较,牛蒡子苷元降低了DSS诱导的结肠组织炎症因子和氧化应激水平。此外,牛蒡子苷元通过降低NF-κB p65磷酸化水平阻断NF-κB通路,进而影响其下游ZO-1蛋白表达。HE染色结果可观察到牛蒡子苷元高剂量给药组小鼠结肠组织损伤显著减轻。结论:牛蒡子苷元通过NF-κB/ZO-1通路调节炎症和氧化应激水平,改善IBD症状。
Objective:To investigate the therapeutic effect and mechanism of arctigenin on inflammatory bowel disease(IBD).Methods:Mice were induced to establish IBD models in vitro and in vivo by LPS stimulation of human intestinal cells Caco-2 and dextran sodium sulfate(DSS).Twenty-four C57BL/6 mice were randomly divided into four groups:blank control group(Control),model group(Model),arctigenin low(10 mg/kg arctigenin)and high(40 mg/kg arctigenin)doses treatment groups.The levels of inflammatory factors TNF-α,IL-1β,IL-6 and oxidative and antioxidant stress markers MDA and SOD in Caco-2 cells and colon tissue of mice were detected by ELISA.The phosphorylation level of NF-κB p65 and the expression of ZO-1 protein in Caco-2 cells and mouse colon were detected by Western blot.Mice were killed on the 9th day of administration,and the histopathological changes of colonic tissue were studied by HE staining.Results:In vitro experiments showed that arctigenin significantly inhibited LPS-induced release of inflammatory factors and reduced oxidative stress level.Western blot results showed that arctigenin reduced the phosphorylation level of NF-κB p65 protein and the expression of ZO-1 protein.In vivo experiments showed that arctigenin reduced the inflammatory factors and oxidative stress levels in colon tissue induced by DSS compared with the model group.In addition,arctigenin reduced the phosphorylation level of NF-κB p65 protein and blocked NF-κB pathway,which affected the expression of ZO-1 protein.HE staining results showed that the colon tissue injury was significantly reduced in arctigenin high dose group.Conclusion:Arctigenin can regulate the levels of inflammation and oxidative stress through NF-κB/ZO-1 pathway,thus improving the symptoms of IBD.
作者
李家驹
黄佑娇
李远迪
何可可
苏敏(指导)
LI Jiaju;HUANG Youjiao;LI Yuandi;HE Keke;SU Min(Basic Medical College,Guizhou Medical University,Guiyang 550025,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2023年第10期2166-2170,共5页
Chinese Journal of Immunology
基金
贵州省科技计划项目(黔科合平台人才[2020]4103号)。
