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Poultry science. 2025 Jun 7;104(9):105409. doi: 10.1016/j.psj.2025.105409 Q14.22025

Effect of luteolin on ceftiofur intestinal absorption: the rational use of Caco-2 monolayer cell model and everted gut sac model

黄酮类化合物鼠李素对头孢曲松肠吸收的影响：体外Caco-2单层细胞模型与翻转肠囊模型的合理应用 翻译改进

Ruxia Wang  1, Zhiruo Kang  1, Mingang Li  1, Zehui Zhang  2, Yuru Guo  1, Shengli Niu  1, Limei Han  1, Chunlian Tian  3, Mingchun Liu  4

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作者单位

  • 1 Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road Shenhe Dist., Shenyang, 110866, PR China.
  • 2 College of Laboratory Animal Medicine, Liaoning University of Traditional Chinese Medicine, 79 Chongshan Road Huanggu Dist., Shenyang, 110847, PR China.
  • 3 Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road Shenhe Dist., Shenyang, 110866, PR China. Electronic address: chunliantian@syau.edu.cn.
  • 4 Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road Shenhe Dist., Shenyang, 110866, PR China. Electronic address: liumingchun@syau.edu.cn.

    • DOI: 10.1016/j.psj.2025.105409 PMID: 40517618

    摘要 中英对照阅读

    Background: The clinical utility of ceftiofur primarily stems from its broad-spectrum antibacterial properties. However, its limited oral bioavailability significantly constrains therapeutic effectiveness. Although natural flavonoids have been well-documented to facilitate intestinal drug transport, the potential of luteolin to enhance ceftiofur intestinal absorption and the mechanistic basis for this effect remain to be eluc... ...点击完成人机验证后继续浏览

    背景： 头孢噻呋的临床实用性主要源于其广谱抗菌特性。然而，其有限的口服生物利用度显著限制了治疗效果。虽然天然黄酮类化合物已被广泛记录为促进肠道药物转运，但鼠李素增强头孢噻呋肠吸收潜力及其机制基础仍有待阐明。

    目的： 本研究旨在探讨鼠李素对鸭子肠道中头孢噻呋吸收的影响，并阐明其分子机制。

    方法： 本研究采用翻转的鸭肠囊和Caco-2细胞单层模型，分别在有无鼠李素存在的情况下检测头孢噻呋的肠道吸收情况。使用维拉帕米（P-糖蛋白，P-gp）、Ko143（乳腺癌耐药蛋白，BCRP）及普鲁卡因胺（多药耐药相关蛋白2，MRP2）特异性抑制剂来识别限制吸收的转运体。采用实时定量PCR (qRT-PCR) 和Western blot方法评估外排转运体和紧密连接蛋白的转录与翻译水平。分子对接分析了鼠李素对关键转运蛋白的结合亲和力。

    结果： 头孢噻呋在鸭子肠道中通过主动运输机制吸收效果较差。重要的是，鼠李素增强了头孢噻呋的肠吸收作用。此外，普鲁卡因胺（MRP2抑制剂）促进了头孢噻呋的肠吸收。qRT-PCR和Western blot检测结果显示，鼠李素下调了与头孢噻呋外排相关的转运体MRP2及紧密连接蛋白（Occludin、Claudin-1和ZO-1）。分子对接结果表明，鼠李素对这些关键转运蛋白表现出较强的结合亲和力。

    结论： 鼠李素通过下调MRP2或紧密连接蛋白(Occludin、Claudin-1 和 ZO-1) 的转录与翻译水平，从而增加头孢噻呋的肠吸收作用，支持其作为口服生物利用度增强剂的作用。

    关键词： 头孢噻呋；肠道吸收；鼠李素；MRP2；紧密连接蛋白。

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    期刊名：Poultry science

    缩写：POULTRY SCI

    ISSN：0032-5791

    e-ISSN：1525-3171

    IF/分区：4.2/Q1

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    Effect of luteolin on ceftiofur intestinal absorption: the rational use of Caco-2 monolayer cell model and everted gut sac model