首页|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

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

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

alcoholic liver diseasesodium butyrateintestinal tight junction proteinsinflammatory cytokines

田文妍、张晓旭、张丽娜、郭米雪、刘健、李婷、杨少奇

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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

宁夏医科大学基础医学院,银川 750004

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

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

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酒精性肝病 丁酸钠 肠道紧密连接蛋白 炎性因子

国家自然科学基金项目国家自然科学基金项目

8160271382160122

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
年,卷(期):2024.46(1)
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