宁夏医科大学学报2024,Vol.46Issue(1) :1-6,14.DOI:10.16050/j.cnki.issn1674-6309.2024.01.001

丁酸钠通过调节肠道通透性改善酒精性肝病小鼠炎症的机制

Mechanistic Study of Sodium Butyrate in Improving Intestinal Permeability and Alcoholic Liver Disease in Mice

田文妍 张晓旭 张丽娜 郭米雪 刘健 李婷 杨少奇
宁夏医科大学学报2024,Vol.46Issue(1) :1-6,14.DOI:10.16050/j.cnki.issn1674-6309.2024.01.001

丁酸钠通过调节肠道通透性改善酒精性肝病小鼠炎症的机制

Mechanistic Study of Sodium Butyrate in Improving Intestinal Permeability and Alcoholic Liver Disease in Mice

田文妍 1张晓旭 1张丽娜 1郭米雪 2刘健 3李婷 4杨少奇5
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作者信息

  • 1. 宁夏医科大学,银川 750004;宁夏医科大学总医院消化内科,宁夏医科大学第一临床医学院,银川 750004
  • 2. 宁夏医科大学基础医学院,银川 750004
  • 3. 宁夏医科大学总医院肝胆外科,宁夏医科大学第一临床医学院,银川 750004
  • 4. 宁夏医科大学总医院儿科,宁夏医科大学第一临床医学院,银川 750004
  • 5. 宁夏医科大学总医院消化内科,宁夏医科大学第一临床医学院,银川 750004
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摘要

目的 探讨丁酸钠通过肠—肝循环改善肠道通透性来降低酒精性肝病(ALD)小鼠的炎性因子水平.方法 将 60 只雌性C57BL/6J小鼠随机分为阴性对照组、ALD模型组、丁酸钠(NaB)干预对照组、NaB干预模型组,每组 15 只.对照组给予Lieber-DeCarli对照液体饲料,模型组给予等热量的Lieber-DeCarli酒精液体饲料,同时NaB干预对照组给予含NaB(0.6 g·kg-1)的液体饲料,喂养 6 周后,收集组织.采用HE染色检测肠道炎性细胞浸润及黏膜完整性;免疫荧光检测肠道紧密连接蛋白ZO-1、Occludin的表达水平;鲎试剂盒检测血浆、肝脏及肠道内毒素(LPS)的水平;ELISA法检测血浆、肝脏及肠道白细胞介素(IL)-6、IL-1β、IL-17A的水平;并分析紧密连接蛋白与肠道炎性因子表达水平的相关性.结果 与阴性对照组相比,HE染色结果显示,ALD模型组小鼠的肠道绒毛结构紊乱;免疫荧光结果显示,紧密连接蛋白表达降低(P<0.05);血浆、肝脏及肠道LPS均升高(P均<0.05);血浆、肝脏及肠道炎性因子水平均升高(P均<0.05).与ALD模型组相比,NaB干预模型组小鼠肠道绒毛结构好转,肠道紧密连接蛋白表达升高,血浆、肝脏及肠道LPS水平降低,血浆、肝脏及肠道的炎性因子水平降低(P均<0.05).相关性分析结果显示,肠道紧密连接蛋白与肠道炎性因子表达水平呈负相关(P<0.05).结论 丁酸钠通过肠—肝循环改善肠道通透性来降低ALD小鼠血浆、肝脏及肠道的炎性因子水平,从而改善ALD小鼠的炎性反应.

Abstract

Objective To investigate the effect of sodium butyrate on the level of inflammatory factors in mice with alcoholic liver disease(ALD)by improving intestinal permeability through enteric-liver circulation.Meth-ods Sixty female C57BL/6J mice were randomly divided into 4 groups:negative control group,ALD model group,sodium butyrate(NaB)-treated control group and NaB-treated ALD model group,15 per group.Mice in the control group were fed with ethanol-free modified Lieber-DeCarli liquid diets,while the model group was fed with ethanol-containing modified Lieber-DeCarli liquid diets.At the same time,the NaB intervention group was fed with liquid feed containing NaB(0.6 g·kg-1),and after 6 weeks of feeding,tissues were collected.HE staining was used to detect intestinal inflammatory cell infiltration and intestinal mucosal integrity.The expres-sion of the intestinal tight junction proteins ZO-1 and Occludin was detected by immunofluorescence.The ex-pression of endotoxin(LPS)in plasma,liver and intestine was detected by limulus amebocyte lysate kit.The ex-pression levels of plasma,liver and intestinal interleukin 6(IL-6),interleukin 1β(IL-1β),and interleukin 17A(IL-17A)were determined by ELISA.The correlation between the tight junction proteins ZO-1 and Occludin with the expression levels of intestinal inflammatory factors(IL-1β,IL-6,IL-17A and LPS)were also analyzed.Results Compared with the negative control group,HE staining results showed in-testinal villus structure of the ALD model group;immunofluorescence results showed decreased expression of tight junction protein(P<0.05);plasma,liver,and intestinal LPS increased(P all<0.05);plasma,liver,and in-testinal inflammatory factor levels increased(P all<0.05).Compared with the ALD model group,intestinal vil-lus structure was increased of the NaB intervention model group;intestinal tight junction protein increased,but plasma,liver and intestinal LPS levels decreased;plasma,liver and intestinal inflammatory factor levels signifi-cantly decreased(Pall<0.05);and correlation analysis results showed negative correlation of intestinal inflam-matory factors(P<0.05).Conclusion Sodium butyrate reduces the levels of inflammatory factors in plasma,liver and intestine of ALD mice by improving intestinal permeability through enteric-liver circulation,thus im-proving the inflammatory response of ALD mice.

关键词

酒精性肝病/丁酸钠/肠道紧密连接蛋白/炎性因子

Key words

alcoholic liver disease/sodium butyrate/intestinal tight junction proteins/inflammatory cytokines

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基金项目

国家自然科学基金项目(81602713)

国家自然科学基金项目(82160122)

出版年

2024
宁夏医科大学学报
宁夏医科大学

宁夏医科大学学报

CSTPCD
影响因子:0.84
ISSN:1674-6309
参考文献量22
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