膳食ALEs肠上皮转运特性与屏障损伤效应研究
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(1.南开大学医学院 天津 300350;2.浙江农林大学食品与健康学院 杭州 214122)

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国家自然科学基金重点项目(32030038)


Study on the Intestinal Epithelial Transport Characteristics and Barrier Damage Effects of Dietary ALEs
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(1.School of Medicine, Nankai University, Tianjin 300350 ;2.School of Food and Health, Zhejiang A&F University, Hangzhou 214122)

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    摘要:

    为探究不同类型膳食高级脂肪氧化终产物(ALEs)在肠道中的吸收特性及其对肠道屏障的影响,采用Caco-2细胞单层吸收模型结合高分辨质谱分析,评估不同结构膳食ALEs的跨膜吸收规律。借助扫描电子显微镜和免疫荧光分析等手段,评估膳食ALEs对肠道屏障功能的影响,并分析肠屏障损伤对ALEs吸收特性的影响。结果表明,结合态ALEs中有6种能够被肠道吸收,包括N-δ-(2-嘧啶基)-L-鸟氨酸、4-甲基-2,6-二氢吡啶-3,5-二甲醛、N末端形成的N-ε-(丙烯醛)结合肽、N末端形成的二氢吡啶型结合肽、N-ε-(1-亚氨基-3-氨基丙烯)赖氨酸和2-鸟氨甲酸基-4-甲基(1-ε-赖氨酸基)1,3-咪唑,这些ALEs主要以二肽或三肽的形式存在。此外,ALEs的存在导致Caco-2细胞单层的表观渗透系数提高了50.83%,跨膜电阻降低了53.28%,并导致紧密连接蛋白Occludin和ZO-1以及黏蛋白Mucin2的表达降低,表明ALEs破坏了肠道屏障的完整性。进一步研究显示,在肠屏障受损的情况下,ALEs的吸收状态发生变化,尤其是DPH-peptide和NP-peptide在肠道中的吸收增加。综上所述,ALEs通过破坏紧密连接蛋白和黏蛋白的表达影响肠道屏障功能。肠道屏障受损时,ALEs的吸收特性发生显著变化,可能影响其在体内的分布和代谢。这些发现对了解ALEs在肠道中的行为及其对肠道屏障损伤的机制具有重要意义,为预防与饮食相关的慢性疾病提供了科学依据。

    Abstract:

    To investigate the absorption characteristics of different types of dietary advanced lipid oxidation end products (ALEs) in the intestine and their effects on intestinal barrier integrity, this study employed a Caco-2 cell monolayer absorption model combined with high-resolution mass spectrometry to evaluate the transmembrane absorption patterns of bound ALEs. Using scanning electron microscopy and immunofluorescence analysis, the study further assessed the impact of dietary ALEs on intestinal barrier function and analyzed how intestinal barrier damage affects ALEs absorption characteristics. The results demonstrated that six types of bound ALEs, namely NPO, DHP-Lys, NP-peptide, DHP-peptide, NIAL and OMLI, can be absorbed in the intestine, primarily existing in dipeptide or tripeptide forms. Moreover, the presence of ALEs increased the apparent permeability coefficient of Caco-2 monolayers by 50.83%, decreased the transmembrane resistance by 53.28%, and led to reduced expression of tight junction proteins Occludin and ZO-1, as well as Mucin2, indicating that ALEs disrupted the integrity of the intestinal barrier. Further investigations revealed that under conditions of compromised intestinal barrier, the absorption states of ALEs change, particularly with increased absorption of DHP-peptide and NP-peptide in the intestine. In summary, ALEs can affect intestinal barrier function by disrupting the expression of tight junction proteins and mucins. When the intestinal barrier is impaired, the absorption characteristics of ALEs significantly alter, potentially affecting their distribution and metabolism in the body. These findings are crucial for understanding the behavior of ALEs in the intestine and their potential mechanisms of intestinal barrier damage, providing scientific evidence for preventing diet-related chronic diseases.

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王娅娅,李远飞,王睿粲,王硕.膳食ALEs肠上皮转运特性与屏障损伤效应研究[J].中国食品学报,2025,25(3):23-32

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  • 收稿日期:2024-11-01
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  • 在线发布日期: 2025-05-23
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