国内团队:褪黑素通过肠-肝轴,改善黄曲霉毒素引起的肝损伤
  • 褪黑素预处理显著增加小鼠肠道紧密连接蛋白的表达,降低肠道通透性,减少肠源性LPS的产生和改善肠道菌群紊乱,最终缓解黄曲霉毒素B1(AFB1)诱导的肝损伤,但抗生素使用阻断此益处;
  • 褪黑素预处理提高了AFB1暴露小鼠回肠法尼酯X受体(FXR)蛋白表达,降低肝脏TLR4/NF-κB信号通路相关mRNA和蛋白(如TLR4、MyD88等)表达;
  • 选择性FXR抑制剂预处理增加了肝脏TLR4/NF-κB信号通路相关mRNA和蛋白表达,可阻断褪黑素对肝损伤的缓解作用。
主编推荐语
注册营养师陈彬林
黄曲霉毒素B1 (AFB1)是一种广泛存在于食品和动物饲料中的污染物,其靶器官是肝脏,是一种强致癌物。近期南京农业大学动物医学院黄克和、刘云欢作为共同通讯作者在Journal of Pineal Research发表的一项研究发现,褪黑素(剂量为20 mg/kg体重)预处理改善了AFB1诱导的小鼠肝损伤,其潜在机制可能与调节肠道菌群/肠道FXR/肝脏TLR4信号轴有关。
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Melatonin mitigates aflatoxin B1-induced liver injury via modulation of gut microbiota/intestinal FXR/liver TLR4 signaling axis in mice

褪黑素通过调节小鼠肠道菌群/肠道FXR/肝脏TLR4信号轴减轻黄曲霉毒素B1诱导的肝损伤

10.1111/jpi.12812

06-02, Article

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Aflatoxin B1 (AFB1) is a widespread contaminant in foods and feedstuffs, and its target organ is the liver. Melatonin (MT) has been shown to alleviate inflammation in organs and remodel gut microbiota in animals and humans. However, the underlying mechanism by which MT alleviates AFB1-induced liver injury remains unclear. In the present study, MT pretreatment markedly increased the expression of intestinal tight junction proteins (ZO-1, Occludin, and Claudin-1), decreased intestinal permeability, reduced production of gut-derived LPS and remodeled gut microbiota, ultimately alleviated AFB1-induced liver injury in mice. Interestingly, MT pretreatment failed to exert beneficial effects on the intestine and liver in antibiotic-treated mice. Meanwhile, MT pretreatment significantly increased the FXR protein expression of ileum, and decreased the TLR4/NF-κB signaling pathway related mRNA and proteins (TLR4, MyD88, p-p65 and p-IκBα) expression in livers of AFB1-exposed mice. Subsequently, pretreatment by Gly-β-MCA, an intestine-selective FXR inhibitor, blocked the alleviating effect of MT on liver injury through increasing the liver-specific expression of TLR4/NF-κB signaling pathway related mRNA and proteins (TLR4, MyD88, p-p65 and p-IκBα). In conclusion, MT pretreatment ameliorated AFB1-induced liver injury and the potential mechanisms may be related to regulate gut microbiota/intestinal FXR/liver TLR4 signaling axis, which provides strong evidence for the protection of gut-derived liver inflammation.

First Authors:
Shuiping Liu

Correspondence Authors:
Yunhuan Liu,Kehe Huang

All Authors:
Shuiping Liu,Weili Kang,Xinru Mao,Lei Ge,Heng Du,Jinyan Li,Lili Hou,Dandan Liu,Yulong Yin,Yunhuan Liu,Kehe Huang

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