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口服补充胆碱可减轻与酒精相关的肝病 (ALD) 的发展。

Oral supplementation of choline attenuates the development of alcohol-related liver disease (ALD).

机构信息

Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Josef-Holaubek-Platz 2 (UZA II), A-1090, Vienna, Austria.

Livestock Microbial Ecology Department, Institute of Animal Science, University of Hohenheim, Stuttgart, Germany.

出版信息

Mol Med. 2024 Oct 18;30(1):181. doi: 10.1186/s10020-024-00950-4.

Abstract

BACKGROUND

Chronic alcohol intake is associated with alterations of choline metabolism in various tissues. Here, we assessed if an oral choline supplementation attenuated the development of alcohol-related liver disease (ALD) in mice.

METHODS

Female C57BL/6 J mice (n = 8/group) were either pair-fed a liquid control diet, or a Lieber DeCarli liquid diet (5% ethanol) ± 2.7 g choline/kg diet for 29 days. Liver damage, markers of intestinal permeability and intestinal microbiota composition were determined. Moreover, the effects of choline on ethanol-induced intestinal permeability were assessed in an ex vivo model.

RESULTS

ALD development as determined by liver histology and assessing markers of inflammation (e.g., nitric oxide, interleukin 6 and 4-hydroxynonenal protein adducts) was attenuated by the supplementation of choline. Intestinal permeability in small intestine being significantly higher in ethanol-fed mice was at the level of controls in ethanol-fed mice receiving choline. In contrast, no effects of the choline supplementation were found on intestinal microbiota composition. Choline also significantly attenuated the ethanol-induced intestinal barrier dysfunction in small intestinal tissue ex vivo, an effect almost entirely abolished by the choline oxidase inhibitor dimbunol.

CONCLUSION

Our results suggest that an oral choline supplementation attenuates the development of ALD in mice and is related to a protection from intestinal barrier dysfunction.

摘要

背景

慢性酒精摄入与各种组织中胆碱代谢的改变有关。在这里,我们评估了口服补充胆碱是否可以减轻小鼠的酒精相关性肝病(ALD)的发展。

方法

雌性 C57BL/6J 小鼠(每组 8 只)分别用液体对照饮食或 Lieber DeCarli 液体饮食(5%乙醇)±2.7g 胆碱/公斤饮食喂养 29 天。测定肝损伤、肠道通透性标志物和肠道微生物组成。此外,还在离体模型中评估了胆碱对乙醇诱导的肠道通透性的影响。

结果

胆碱补充可减轻肝组织学和炎症标志物(如一氧化氮、白细胞介素 6 和 4-羟基壬烯醛蛋白加合物)所确定的 ALD 发展。在乙醇喂养的小鼠中,小肠通透性显著升高,而在接受胆碱的乙醇喂养的小鼠中,其水平与对照组相当。相比之下,胆碱补充对肠道微生物组成没有影响。胆碱还可显著减轻离体小肠组织中乙醇诱导的肠道屏障功能障碍,而胆碱氧化酶抑制剂二苯并呋喃几乎完全消除了这种作用。

结论

我们的结果表明,口服补充胆碱可减轻小鼠的 ALD 发展,并与保护肠道屏障功能有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c2b/11488139/8aa6d7a6b8c9/10020_2024_950_Fig1_HTML.jpg

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