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通过靶向Toll样受体来重新平衡肠道微生物群,是否有可能早期干预肝硬化?

Is it possible to intervene early cirrhosis by targeting toll-like receptors to rebalance the intestinal microbiome?

作者信息

Zhang Jiaxin, Zao Xiaobin, Zhang Jiaying, Guo Ziwei, Jin Qian, Chen Guang, Gan Da'nan, Du Hongbo, Ye Yong'an

机构信息

Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China; Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing, China.

School of Mechanical Engineering and Automation, Beihang University, Beijing, China.

出版信息

Int Immunopharmacol. 2023 Feb;115:109627. doi: 10.1016/j.intimp.2022.109627. Epub 2022 Dec 26.

Abstract

Cirrhosis is a progressive chronic liver disease caused by one or more causes and characterized by diffuse fibrosis, pseudolobules, and regenerated nodules. Once progression to hepatic decompensation, the function of the liver and other organs is impaired and almost impossible to reverse and recover, which often results in hospitalization, impaired quality of life, and high mortality. However, in the early stage of cirrhosis, there seems to be a possibility of cirrhosis reversal. The development of cirrhosis is related to the intestinal microbiota and activation of toll-like receptors (TLRs) pathways, which could regulate cell proliferation, apoptosis, expression of the hepatomitogen epiregulin, and liver inflammation. Targeting regulation of intestinal microbiota and TLRs pathways could affect the occurrence and development of cirrhosis and its complications. In this paper, we first reviewed the dynamic change of intestinal microbiota and TLRs during cirrhosis progression. And further discussed the interaction between them and potential therapeutic targets to reverse early staged cirrhosis.

摘要

肝硬化是一种由一种或多种病因引起的进行性慢性肝病,其特征为弥漫性纤维化、假小叶和再生结节。一旦进展至肝失代偿期,肝脏及其他器官的功能就会受损,几乎无法逆转和恢复,这常常导致住院治疗、生活质量下降以及高死亡率。然而,在肝硬化的早期阶段,似乎存在肝硬化逆转的可能性。肝硬化的发展与肠道微生物群以及Toll样受体(TLRs)通路的激活有关,这些因素可调节细胞增殖、凋亡、肝有丝分裂原表皮调节素的表达以及肝脏炎症。针对肠道微生物群和TLRs通路进行调控可能会影响肝硬化及其并发症的发生和发展。在本文中,我们首先回顾了肝硬化进展过程中肠道微生物群和TLRs的动态变化。并进一步探讨了它们之间的相互作用以及逆转早期肝硬化的潜在治疗靶点。

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