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姜黄素通过抑制 NLRP3 炎性小体和调节 TLR4/NF-κB 信号通路来减轻黄曲霉毒素 B1 诱导的鸭子回肠损伤。

Curcumin attenuates aflatoxin B1-induced ileum injury in ducks by inhibiting NLRP3 inflammasome and regulating TLR4/NF-κB signaling pathway.

机构信息

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.

College of Life Science, Yantai University, Yantai City, 264005, Shandong Province, China.

出版信息

Mycotoxin Res. 2024 May;40(2):255-268. doi: 10.1007/s12550-024-00524-7. Epub 2024 Feb 24.

DOI:10.1007/s12550-024-00524-7
PMID:38400893
Abstract

Aflatoxin B1 (AFB1) is a widespread toxic contamination in feed for animals. The primary active component of turmeric, curcumin (Cur), is an antioxidant and an anti-inflammatory. However, it is yet unknown how AFB1 affects the intestinal epithelial barrier and whether Cur acts as a protective mechanism when exposed to AFB1. Here, we explored the mechanism of AFB1-induced intestinal injury from intestinal epithelial barrier, inflammation, pyroptosis, and intestinal flora, and evaluated the protective role of Cur. We found that AFB1 caused weight loss and intestinal morphological damage that is mainly characterized by shortened intestinal villi, deepened crypts, and damaged intestinal epithelium. Exposure to AFB1 decreased the expression of Claudin-1, MUC2, ZO-1, and Occludin and increased the expression of pyroptosis-related factors (NLRP3, GSDMD, Caspase-1, IL-1β, and IL-18) and inflammation-related factors (TLR4, NF-κB, IκB, IFN-γ, and TNF-α). Furthermore, ileal gut microbiota was altered, and simultaneously, the Lactobacillus abundance was decreased. The gut microbiota interacts with a wide range of physiologic functions and disease development in the host through its metabolites, and disturbances in gut microbial metabolism can cause functional impairment of the ileum. Meanwhile, Cur can ameliorate histological ileum injuries and intestinal flora disturbance caused by AFB1. We found that Cur reversed the effects of AFB1 through modulating both NLRP3 inflammasome and the TLR4/NF-κB signaling pathway. In conclusion, AFB1 can induce inflammatory damage and pyroptosis in duck ileum, while Cur has obviously protective effects on all the above damages.

摘要

黄曲霉毒素 B1(AFB1)是动物饲料中广泛存在的有毒污染物。姜黄的主要活性成分姜黄素(Cur)是一种抗氧化剂和抗炎剂。然而,目前尚不清楚 AFB1 如何影响肠道上皮屏障,以及当暴露于 AFB1 时 Cur 是否作为一种保护机制。在这里,我们探讨了 AFB1 诱导的肠道损伤的机制,包括肠道上皮屏障、炎症、细胞焦亡和肠道菌群,并评估了 Cur 的保护作用。我们发现 AFB1 导致体重减轻和肠道形态损伤,主要表现为肠绒毛缩短、隐窝加深和肠上皮损伤。暴露于 AFB1 会降低 Claudin-1、MUC2、ZO-1 和 Occludin 的表达,增加细胞焦亡相关因子(NLRP3、GSDMD、Caspase-1、IL-1β 和 IL-18)和炎症相关因子(TLR4、NF-κB、IκB、IFN-γ 和 TNF-α)的表达。此外,回肠肠道微生物群发生改变,同时,乳杆菌丰度降低。肠道微生物群通过其代谢产物与宿主的广泛生理功能和疾病发展相互作用,肠道微生物代谢紊乱可导致回肠功能障碍。同时,Cur 可以改善 AFB1 引起的回肠组织学损伤和肠道菌群紊乱。我们发现 Cur 通过调节 NLRP3 炎症小体和 TLR4/NF-κB 信号通路来逆转 AFB1 的作用。总之,AFB1 可诱导鸭回肠炎症损伤和细胞焦亡,而 Cur 对所有上述损伤均具有明显的保护作用。

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本文引用的文献

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