摘要
目的 探讨丁酸钠(sodium butyrate, NaB)对葡聚糖硫酸钠(dextran sulfate sodium salt,DSS)诱导的炎症性肠病模型小鼠保护作用及其机制。方法 将36只6 w龄C57BL/6J小鼠随机分为对照组(Control)、模型组(Model)、NaB(500 mg/kg.d ip)干预组和阳性治疗药物5-氨基水杨酸(5-aminosalicylic acid,5-ASA)干预组(150mg/kg.d ig)。造模开始前使用NaB预处理12 d并直至实验结束,造模期间饮用2.5%DSS水溶液持续8 d后换回高压灭菌水饮用3d处死并量取结肠长度及脾脏重量。比较小鼠体重、生存率与疾病活动指数,H&E染色观察小鼠结肠及脾脏病理学改变,RT-PCR检测结肠炎症因子TNF-α、IL-6、IL-1β的mRNA表达,检测结肠Nrf2和NFκB的mRNA表达及p65的蛋白磷酸化水平。结果 与正常对照组相比,模型组小鼠体重与生存率明显下降、疾病活动指数明显升高、脾脏重量明显增加并且结肠长度明显缩短(P<0.001),HE染色显示结肠与脾脏炎性细胞浸润,结肠炎症因子表达显著增加(P<0.001),Nrf2基因表达显著下调(P<0.001),NFκB的基因表达与磷酸化水平显著上升(P<0.001、P<0.01);与模型组相比,NaB干预组与阳性治疗药物组小鼠生存率、疾病活动指数、脾脏重量、结肠长度、炎症因子等指标显著改善(P<0.05、P<0.001),结肠与脾脏病理改变减轻,Nrf2基因表达上调(P<0.05)而NFκB的基因表达与磷酸化水平抑制(P<0.05、P<0.01)结论 NaB对炎症性肠病具有保护作用,其机制可能与Nrf2的激活以及NFκB的抑制有关。[营养学报,2022,44(1):52-78]
To investigate the effect of sodium butyrate(NaB) on inflammatory bowel disease(IBD) induced by dextran sulfate sodium salt(DSS) in mice and the mechanism of action. Methods Thirty-six 6-week-old C57BL/6J mice were randomly divided into control group, model group, NaB(500 mg/kg.d ip) intervention group and 5-aminosalicylic acid(5-ASA) intervention group(150 mg/kg.d ig). NaB was used for pretreatment for 12 days before modeling and throughout the experiment. After drinking 2.5% DSS aqueous solution for 8 days, mice were given autoclaved water for 3 days, and then sacrificed. Colon length and spleen weight were measured. The body weight, survival rate and disease activity index were compared. The pathological changes of colon and spleen were observed after H&E staining. The mRNA expressions of inflammatory factors TNF-α, IL-6 and IL-1β were detected by RT-PCR, and the mRNA expressions of Nrf2 and NFκB and protein phosphorylation of P65 were also detected. Results Compared with the control group, the body weight and survival rate of the model group were significantly decreased, disease activity index was significantly increased, spleen weight was significantly increased and colon length was significantly shortened(P<0.001). HE staining showed infiltration of inflammatory cells in colon and spleen, and the expression of inflammatory factors in colon was significantly increased(P<0.001). Nrf2 gene expression was significantly down-regulated(P<0.001), and NFκB gene expression and phosphorylation level were significantly increased(P<0.001, P<0.01). Compared with the model group, survival rate, disease activity index, spleen weight, colon length, inflammatory factors and other indicators in the NaB intervention group and 5-ASA group were significantly improved(P<0.05, P<0.001), and pathological changes of colon and spleen were reduced.The expression of Nrf2 gene was up-regulated(P<0.05), while the expression of NFκB gene was inhibited(P<0.05, P<0.01).Conclusion NaB has a protective effect on inflammatory bowel disea
作者
卞中博
张秋玉
秦勇
孙小蝶
刘华缓
毛联智
孙素霞
BIAN Zhong-bo;ZHANG Qiu-yu;QIN Yong;SUN Xiao-die;LIU Hua-huan;MAO Lian-zhi;SUN Su-xia(Department of Nutrition and Food Hygiene,School of Public Health,Southern Medical University,Guangzhou 510515,China)
出处
《营养学报》
CAS
CSCD
北大核心
2022年第1期72-78,共7页
Acta Nutrimenta Sinica
基金
国家自然科学基金(No.81773429)
广东省自然科学基金(No.2022A1515011631)。
