高糖、高脂饮食对小鼠肠道屏障功能及炎症的影响
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(上海理工大学 上海 200093)

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国家重点研发计划项目(2018YFC1604305);上海市科技兴农重点项目(2019-02-08-00-07-F01152);上海市大学生创新创业项目(SH 2020170)


Effect of High Sugar and High Fat Diet on Intestinal Barrier Function and Inflammation in Mice
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(University of Shanghai for Science and Technology, Shanghai 200093)

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    摘要:

    目的:研究高糖、高脂饮食(HSFD)对肠道屏障功能以及炎症水平的影响。方法:选取SPF级C57BL/6J鼠进行HSFD干预4周,以低糖、低脂饮食(LFD)作为对照,测定血脂相关指标、肠道通透性、炎症水平以及相关紧密连接蛋白表达变化。结果:与LFD相比,HSFD喂养下,小鼠总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)等血脂指标分别升高74%,34%,105%(P<0.05),高密度脂蛋白胆固醇(HDL-C)含量降低36%(P<0.01),肝脏病理染色显示脂肪细胞异常聚集,表明HSFD干预造成小鼠肝脏脂质代谢紊乱。对小鼠结肠炎症症状分析显示,HSFD小鼠粪便有带血情况,疾病活动指数评分(DAI)、结肠组织髓过氧化物酶(MPO)活性显著提高(P<0.05),实时荧光定量PCR和酶联免疫(ELISA)法测得结肠组织中肿瘤坏死因子(TNF-α)炎症因子表达显著提高(P<0.05),说明HSFD小鼠肠道处于轻度炎症状态。对肠道屏障功能分析显示,HSFD小鼠结肠上皮组织发生炎症性细胞浸润,隐窝结构被破坏,杯状细胞减少,闭合小环蛋白(ZO-1)、咬合蛋白(Occludin)、黏液蛋白(MUC-2)等屏障相关蛋白的基因表达水平显著降低(P<0.05)。免疫荧光结果显示,HSFD小鼠结肠组织中ZO-1、Occludin表达水平显著降低(P<0.05)。异硫氰酸荧光素标记葡聚糖(FITC-Dextran)分析显示HSFD小鼠肠道通透性显著增加。结论:HSFD会导致小鼠脂质代谢紊乱,破坏肠道屏障功能,促使肠道处于炎症状态,从而可能引起肠道慢性病变。

    Abstract:

    Objective: The way of eating has an important influence on the intestinal immunity and inflammatory environment. This article examines the effects of high-sugar and high-fat diet (HSFD) on the intestinal barrier function and the level of inflammation. Methods: In the experiment, SPF grade C57BL/6J mice were selected for HSFD intervention for 4 weeks. At the same time, low-sugar and low-fat diet (LFD) was used as a control to determine blood lipid-related indicators, intestinal permeability, inflammation levels, and related tight junction protein expression changes. Results: Under HSFD conditions, the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and other blood lipid indexes of mice increased significantly (P<0.05), and high-density lipoprotein cholesterol (HDL-C) The content was significantly reduced(P<0.01), and the pathological staining of the liver showed abnormal accumulation of adipocytes, indicating that the intervention of HSFD caused the disorder of lipid metabolism in the liver of mice. Further analysis of the symptoms of colon inflammation in mice showed that HSFD mice had blood in the stool, disease activity index (DAI) and colon tissue myeloperoxidase (MPO) activity were significantly increased (P<0.05), real-time fluorescent quantitative PCR (Quantitative Real-time PCR) and enzyme-linked immunoassay (ELISA) methods showed that the expression of tumor necrosis factor (TNF-α) inflammatory factors in colon tissue was significantly increased (P<0.05), indicating that the intestinal tract of HSFD mice is in a mildly inflammatory state. The analysis of the intestinal barrier function showed that inflammatory cell infiltration occurred in the colonic epithelial tissue of HSFD mice, the crypt structure was destroyed, the goblet cells were reduced, the occluding protein (ZO-1), the occluding protein (Occludin), and the mucus protein (the gene expression levels of barrier-related proteins such as MUC-2) were significantly reduced (P<0.05). The immunofluorescence results showed that the expression levels of ZO-1 and Occludin in the colon tissue of HSFD mice were significantly reduced (P<0.05). Fluorescein isothiocyanate-labeled dextran (FITC-Dextran) analysis showed that the intestinal permeability of HSFD mice was significantly increased. Conclusion: HSFD can cause lipid metabolism disorders in mice, destroy the intestinal barrier function, and promote the intestinal tract to be in a state of inflammation, which may cause chronic intestinal lesions.

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邵君琳,田苗新,王富康,孙奕炜,王光强,艾连中,夏永军.高糖、高脂饮食对小鼠肠道屏障功能及炎症的影响[J].中国食品学报,2023,23(9):79-88

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  • 收稿日期:2022-09-18
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  • 在线发布日期: 2023-11-22
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