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柚皮素缓解ETEC诱导小鼠腹泻的作用及机制研究

Study on the effect and mechanism of naringenin in alleviating diarrhea induced by ETEC in mice
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摘要 为探明柚皮素对产肠毒素大肠杆菌(Enterotoxigenic Escherichia coli,ETEC)感染诱导小鼠腹泻的缓解作用及其相关机制。本试验将40只六周龄雌性ICR小鼠随机分为空白组、柚皮素高(200 mg/kg)、中(150 mg/kg)、低(100 mg/kg)剂量组和模型组(n=8)。柚皮素各剂量处理组连续灌服14 d,空白组和模型组灌服同等体积生理盐水,灌服第15天时,模型组和柚皮素各剂量处理组通过腹腔注射ETEC攻毒。结果表明,与模型组相比,高剂量柚皮素处理组可显著提高小鼠体重,缓解小鼠腹泻,降低死亡率。高剂量柚皮素可显著提高小鼠肠道中紧密连接蛋白和黏蛋白的表达水平,HE染色分析可知柚皮素处理组小鼠在ETEC攻毒后,肠道绒毛结构更加完整,隐窝清晰可见,表明柚皮素对小鼠肠道屏障的完整性具有保护作用,增强了肠道的机械屏障。同时,柚皮素处理显著提高小鼠的脾脏指数,表明提高了机体的免疫功能。高剂量柚皮素处理可显著降低ETEC攻毒后小鼠肠道组织中促炎因子IL-18、IL-6和TNF-α的mRNA表达水平,显著上调肠液中分泌型免疫球蛋白SIgA的表达水平,增强了肠道的免疫屏障。综上所述,本研究发现柚皮素对小鼠肠道机械屏障和免疫屏障具有保护作用,能够改善ETEC诱导的腹泻,且以200 mg/kg给药剂量为最佳,为幼龄动物大肠杆菌腹泻的防治提供了新的策略。 The purpose of this study was to explore the alleviating effect of naringenin on diarrhea induced by Enterotoxigenic Escherichia coli(ETEC)infection in mice and its related mechanisms.In this experiment,40 sixweek-old female ICR mice were randomly divided into a blank group,a high-dose naringenin group(200 mg/kg),a medium-dose naringenin group(150 mg/kg),a low-dose naringenin group(100 mg/kg),and a model group(n=8).The mice in each naringenin treatment group were intragastrically administered for 14 consecutive days,while the blank group and the model group were given the same volume of normal saline.On the 15th day,the model group and the naringenin treatment groups at different doses were challenged by intraperitoneal injection of ETEC.The results showed that the high-dose naringenin treatment significantly increased the body weight of mice,relieved diarrhea in mice,and reduced the mortality rate compared with the model group.High-dose naringenin significantly increased the expression levels of tight junction proteins and mucin in the intestines of mice.According to the analysis of HE staining,after being challenged by ETEC,the intestinal villus structure in the naringenin treatment group was more intact and the crypts were clearly visible,indicating that naringenin had a protective effect on the integrity of the intestinal barrier in mice and enhanced the mechanical barrier of the intestine.Meanwhile,naringenin treatment significantly increased the spleen index of mice,suggesting that it improved the immune function of the body.Highdose naringenin treatment could significantly reduce the mRNA expression levels of pro-inflammatory factors IL-18,IL-6,and TNF-αin the intestinal tissues of mice after being challenged by ETEC,and significantly upregulate the expression level of secretory immunoglobulin A(SIgA)in the intestinal fluid,enhancing the immune barrier of the intestine.In conclusion,this study found that naringenin had a protective effect on the mechanical barrier and immune barriers of the intestine in mice to improve diarrhea induced by ETEC with an optimal dosage as 200 mg/kg,which provides new strategies for the prevention and treatment of Escherichia coli-induced diarrhea in young animals.
作者 姜朋欣 崔亚男 刘濮毓 陈宁 刘康平 李妍 JIANG Pengxin;CUI Yanan;LIU Puyu;CHEN Ning;LIU Kangping;LI Yan(College of Veterinary Medicine,Hebei Agricultural University,Baoding 071001,China)
出处 《河北农业大学学报》 北大核心 2025年第3期91-97,共7页 Journal of Hebei Agricultural University
基金 国家自然科学基金项目(32202803).
关键词 柚皮素 ETEC 肠道屏障 腹泻 naringenin ETEC intestinal barrier diarrhea
作者简介 第一作者:姜朋欣(1999-),女,河北邢台人,硕士研究生,从事幼龄动物细菌性腹泻方面的研究.E-mail:1847350502@qq.com;通信作者:李妍(1987-),女,河北保定人,博士,副教授,从事幼龄动物细菌性腹泻方面的研究.E-mail:dyly@hebau.edu.cn。
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