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炎症性肠病对硬化性胆管炎严重程度的保护作用。

A protective effect of inflammatory bowel disease on the severity of sclerosing cholangitis.

机构信息

Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

Front Immunol. 2024 Mar 6;15:1307297. doi: 10.3389/fimmu.2024.1307297. eCollection 2024.

Abstract

BACKGROUND

Primary sclerosing cholangitis (PSC) is a chronic liver disease marked by inflammation of the bile ducts and results in the development of strictures and fibrosis. A robust clinical correlation exists between PSC and inflammatory bowel disease (IBD). At present, published data are controversial, and it is yet unclear whether IBD drives or attenuates PSC.

METHODS

-deficient mice or DDC-fed mice were used as experimental models for sclerosing cholangitis. Additionally, colitis was induced in mice with experimental sclerosing cholangitis, either through infection with or by feeding with DSS. Lastly, fibrosis levels were determined through FibroScan analysis in people with PSC and PSC-IBD.

RESULTS

Using two distinct experimental models of colitis and two models of sclerosing cholangitis, we found that colitis does not aggravate liver pathology, but rather reduces liver inflammation and liver fibrosis. Likewise, people with PSC-IBD have decreased liver fibrosis compared to those with PSC alone.

CONCLUSIONS

We found evidence that intestinal inflammation attenuates liver pathology. This study serves as a basis for further research on the pathogenesis of PSC and PSC-IBD, as well as the molecular mechanism responsible for the protective effect of IBD on PSC development. This study could lead to the discovery of novel therapeutic targets for PSC.

摘要

背景

原发性硬化性胆管炎(PSC)是一种慢性肝病,其特征为胆管炎症,并导致狭窄和纤维化的发展。PSC 与炎症性肠病(IBD)之间存在很强的临床相关性。目前,已发表的数据存在争议,尚不清楚 IBD 是驱动还是减轻 PSC 的发展。

方法

使用 Il10-/- 缺陷小鼠或 DDC 喂养的小鼠作为硬化性胆管炎的实验模型。此外,通过感染 或用 DSS 喂养,在患有实验性硬化性胆管炎的小鼠中诱导结肠炎。最后,通过 FibroScan 分析在 PSC 和 PSC-IBD 患者中测定纤维化水平。

结果

使用两种不同的结肠炎实验模型和两种硬化性胆管炎模型,我们发现结肠炎不会加重肝病理,但会减轻肝炎症和肝纤维化。同样,PSC-IBD 患者的肝纤维化程度低于单独 PSC 患者。

结论

我们有证据表明肠道炎症减轻了肝病理。这项研究为进一步研究 PSC 和 PSC-IBD 的发病机制以及 IBD 对 PSC 发展的保护作用的分子机制提供了基础。这项研究可能会发现 PSC 的新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1208/10950911/be00bba908dc/fimmu-15-1307297-g001.jpg

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