封堵器
TLR4型
褪黑素
肠道菌群
肝损伤
法尼甾体X受体
生物
脂多糖
内分泌学
信号转导
内科学
促炎细胞因子
炎症
肠道通透性
回肠
紧密连接
免疫学
生物化学
细胞生物学
医学
转录因子
核受体
基因
作者
Shuiping Liu,Weili Kang,Xinru Mao,Lei Ge,Heng Du,Jinyan Li,Lili Hou,Dandan Liu,Yulong Yin,Yunhuan Liu,Kehe Huang
摘要
Abstract 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 Lipopolysaccharide (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 farnesoid X receptor (FXR) protein expression of ileum, and decreased the TLR4/NF‐κB signaling pathway‐related messenger RNA (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 mechanism may be related to regulate gut microbiota/intestinal FXR/liver TLR4 signaling axis, which provides a strong evidence for the protection of gut‐derived liver inflammation.
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