KHK参与高脂高果糖饮食对肠黏膜屏障的损害  

KHK involved in intestinal barrier impairment by high-fat and high-fructose diet

作　　者：杜梦宇 何姝璿 杨岚[1] 胡娟 蒋世秋 檀佳璐 王强[1] 李岩松 DU Mengyu;HE Shuxuan;YANG Lan;HU Juan;JIANG Shiqiu;TAN Jialu;WANG Qiang;LI Yansong(Department of Anesthesiology&Center for Brain Science,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院麻醉手术部&脑科学中心,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2023年第5期731-736,共6页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省自然科学基金青年项目(No.2022JQ-819);国家自然科学基金资助项目(No.81974540)。

摘　　要：目的探究高脂高果糖饮食对小鼠肠黏膜屏障的影响,以及果糖代谢的关键酶果糖激酶(ketohexokinase,KHK)在肠黏膜屏障损伤过程中的作用。方法将8周龄的雄性C57BL/6J小鼠以及Khk^(-/-)小鼠随机分为正常饮食组(ND)、正常饮食+Khk^(-/-)组(ND+Khk^(-/-))、高脂高果糖饮食组(HFHFD)和高脂高果糖饮食+Khk^(-/-)组(HFHFD+Khk^(-/-)),每组8只。在高脂高果糖饮食及正常饮食期间,记录各组小鼠的体质量变化。干预结束后检测各组小鼠血糖、胰岛素水平。通过检测各组小鼠肠道含水量、通透性、紧密连接蛋白表达、血清及肠道炎症因子水平等指标,评估各组小鼠的肠黏膜屏障功能及体内炎症水平。结果相比ND组,HFHFD组小鼠的体质量、血糖、胰岛素水平升高,且小鼠肠道含水量和肠道通透性增加,紧密连接蛋白表达下降,血清及肠道炎症因子水平升高。与HFHFD组相比,HFHFD+Khk^(-/-)组小鼠体质量、血糖、胰岛素水平下降,肠道屏障损伤及肠道炎症明显改善。结论果糖代谢关键酶KHK参与了高脂高果糖饮食对肠黏膜屏障的损伤,Khk基因敲除可显著改善肠道屏障损伤和炎症情况。Objective To explore the effect of high-fat and high-fructose diet on mouse intestinal barrier function,as well as the role of ketohexokinase(KHK),the key enzyme in fructose metabolism,in intestinal barrier impairment.Methods Eight-week-old male control C57BL/6J mice and Khk^(-/-)mice were randomly divided into control+normal diet(ND),control+high-fat and high-fructose diet(HFHFD),Khk^(-/-)+normal diet(ND+Khk^(-/-)),and Khk^(-/-)+high-fat and high-fructose diet(HFHFD+Khk^(-/-))groups,with eight mice in each group.During the high-fat and high-fructose diet and normal diet,the body weight changes of mice in different groups were recorded.After the intervention,the blood glucose and insulin levels of mice in each group were detected.The intestinal barrier function and inflammation level of mice were evaluated by detecting intestinal water content,permeability,tight junction protein expression,serum and intestinal inflammatory factor levels.Results Compared with ND group,HFHFD group significantly increased the body weight,blood glucose and insulin levels of mice,increased the intestinal water content and permeability,decreased the expression of tight junction proteins,and increased inflammatory factors of the serum and intestines.In the two groups fed with high-fat and high-fructose diet,the body weight,blood glucose and insulin levels of the HFHFD+Khk^(-/-)group were significantly lower than those of HFHFD group,and the intestinal barrier dysfunction and inflammation were significantly improved.Conclusion KHK,a key enzyme in fructose metabolism,is involved in the impairment of intestinal barrier caused by high-fat and high-fructose diet.Knockout of Khk gene significantly improved intestinal barrier dysfunction and the inflammation level.

关 键 词：果糖激酶 果糖 肥胖 糖尿病 肠黏膜屏障 

分 类 号：R333.3[医药卫生—人体生理学]