丁酸钠对幼鼠回肠发育、炎症因子及物理屏障功能的调控作用  

The Regulatory Effects of Sodium Butyrate on Ileal Development,Inflammatory Factors and Physical Barrier Function in Young Mice

作　　者：张萱 杨雪 李新科 郑楠[1,2] 孟璐[1,2] ZHANG Xuan;YANG Xue;LI Xinke;ZHENG Nan;MENG Lu(Key Laboratory of Quality&Safety Control for Dairy Products of China Ministry of Agriculture and Rural Affairs,Institute of Animal Sciences,Chinese Academy of Agricultural Sciences,Beijing 100193,China;Laboratory of Quality and Safety Risk Assessment for Dairy Products of China Ministry of Agriculture and Rural Affairs(Beijing),Institute of Animal Sciences,Chinese Academy of Agricultural Sciences,Beijing 100193,China)

机构地区：[1]中国农业科学院北京畜牧兽医研究所农业农村部奶及奶制品质量安全控制重点实验室,北京100193 [2]中国农业科学院北京畜牧兽医研究所农业农村部奶产品质量安全风险评估实验室(北京),北京100193

出　　处：《畜牧兽医学报》2025年第3期1278-1289,共12页ACTA VETERINARIA ET ZOOTECHNICA SINICA

基　　金：国家重点研发计划(2022YFD1600104);中国农业科学院科技创新工程(ASTIP-IAS12);国家现代农业产业技术体系(CARS36)。

摘　　要：旨在利用细胞试验确定丁酸钠对人小肠上皮细胞(FH S 74 int cells)中细胞因子和紧密连接蛋白表达调控的最适浓度,并进一步探讨在该浓度范围下丁酸钠对幼鼠回肠发育、炎症因子及物理屏障功能的影响。细胞试验选取FHs 74 int细胞,探究不同浓度丁酸钠对细胞活力、炎症因子及紧密连接蛋白表达水平的影响。动物试验选取刚出生的C57BL/6J幼鼠,共32只,随机分为4组,每组8只,分别为对照组(0.9%生理盐水)、SB20组(20 mg·kg^(-1)BW丁酸钠)、SB350组(350 mg·kg^(-1)BW丁酸钠)和SB1000组(1000 mg·kg^(-1)BW丁酸钠),连续给药30 d后对幼鼠体重、血常规以及回肠组织学形态、回肠细胞因子和紧密连接蛋白基因表达水平进行检测。在细胞试验中,12.5、25 mmol·L^(-1)丁酸钠显著提高了细胞闭锁蛋白(occludin)的基因和蛋白表达量,25 mmol·L^(-1)丁酸钠显著上调了细胞GPR 109A的基因表达量以及闭锁小带蛋白(ZO^(-1))的基因和蛋白表达量。在动物试验中各组幼鼠的体增重以及血常规指标均无显著差异。通过回肠病理学发现,350 mg·kg^(-1)BW丁酸钠显著提高了幼鼠的回肠绒毛高度,降低了隐窝深度,同时提高了回肠抗炎因子IL-4、IL^(-1)0的mRNA相对表达量,降低促炎因子IL^(-1)8的mRNA相对表达量;1000 mg·kg^(-1)BW丁酸钠显著提高了回肠绒毛高度/隐窝深度的比值(P<0.05),降低隐窝深度和促炎因子TNF-α的mRNA相对表达量。综上,25 mmol·L^(-1)的丁酸钠能够促进FH S 74 int细胞occludin和ZO^(-1)以及GPR 109A的基因表达,维护屏障功能;350 mg·kg^(-1)BW的丁酸钠能够促进幼鼠回肠形态结构发育,提高回肠绒毛高度,降低隐窝深度,同时调节肠道炎症因子和紧密连接蛋白的基因表达。The purpose of this study was to determine the optimal concentration of sodium butyrate in regulating the expression of cytokines and tight junction proteins in human intestinal epithelial cells(FH_(S) 74 int cells)by cell experiments,and to further explore the effects of sodium butyrate on ileum development,inflammatory factors and physical barrier function in young rats.In cell experiments,FH_(S) 74 int cells were selected to explore the effects of different concentrations of sodium butyrate on cell viability,expression levels of inflammatory factors and tight junction protein.In animal experiment,32 newborn C57BL/6J mice were randomly divided into 4 groups,each with 8 mice,namely the control group(0.9%normal saline),SB20 group(20 mg·kg^(-1) BW sodium butyrate),SB350 group(350 mg·kg^(-1) BW sodium butyrate),and SB1000 group(1000 mg·kg^(-1) BW sodium butyrate).After continuous administration for 30 days,body weight,blood routine,ileal histological morphology,ileal cytokine and tight junction protein gene expression levels of mice were detected.In vitro,12.5 and 25 mmol·L^(-1) sodium butyrate increased the gene and protein expression of occludin in cells,and 25 mmol·L^(-1) sodium butyrate significantly increased the gene expression of GPR 109A and the gene and protein expression of ZO-1.In animal experiment,there were no significant differences in body weight and blood routine indexes among the groups of mice.Through ileal pathology,it was found that 350 mg·kg^(-1) BW sodium butyrate significantly increased the ileal villus height but reduce the crypt depth of young mice(P<0.05).At the same time,it increased the relative mRNA expression of ileal anti-inflammatory factors IL-4 and IL-10,while decreasing the relative mRNA expression of pro-inflammatory factor IL-18.1000 mg·kg^(-1) BW sodium butyrate significantly increased the ratio of villus height to crypt depth of ileum(P<0.05),decreased the crpyt depth and the relative mRNA expression of pro-inflammatory factor TNF-α.In conclusion,25 mmol·L^(-1) sodium

关 键 词：丁酸钠 FH S 74 int细胞 肠道屏障 紧密连接蛋白 

分 类 号：S815.7[农业科学—畜牧学]