肝纤维化是大多数慢性肝病中常见的病理。自噬是溶酶体介导的细胞内分解代谢和再循环过程，在维持正常肝功能中发挥着重要作用。核因子红细胞 2 样 2 (Nrf2) 是一种负责调节细胞抗氧化应激反应的转录因子。本研究旨在评估间充质干细胞衍生的外泌体（MSC-exos）对四氯化碳（CCL4）诱导的肝纤维化中内皮间质转化（EMT）的细胞保护作用。大鼠每周两次接受 0.1 ml CCL4 治疗，持续 8 周，然后给予单剂量 MSC-exos。 4 周后处死大鼠，收集肝脏样本用于基因表达分析、蛋白质印迹、组织学研究、免疫组织化学和透射电子显微镜。我们的结果表明，MSC-exos 给药减少了胶原沉积、细胞凋亡和炎症。外泌体调节 Nrf2/Keap1/p62 途径，通过调节 Nrf2/Keap1/p62 的非经典途径恢复自噬和 Nrf2 水平。此外，MSC-exos 调节 miR-153-3p、miR-27a、miR-144 和 miRNA-34a 的表达。总之，本研究揭示了 MSC-exos 作为一种细胞保护剂，对抗慢性肝脏炎症中的 EMT 和肿瘤发生。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Hepatic fibrosis is a common pathology present in most chronic liver diseases. Autophagy is a lysosome-mediated intracellular catabolic and recycling process that plays an essential role in maintaining normal hepatic functions. Nuclear factor erythroid 2-like 2 (Nrf2) is a transcription factor responsible for the regulation of cellular anti-oxidative stress response. This study was designed to assess the cytoprotective effect of mesenchymal stem cell-derived exosomes (MSC-exos) on endothelial-mesenchymal transition (EMT) in Carbon Tetrachloride (CCL4) induced liver fibrosis. Rats were treated with 0.1 ml of CCL4 twice weekly for 8 weeks, followed by administration of a single dose of MSC-exos. Rats were then sacrificed after 4 weeks, and liver samples were collected for gene expression analyses, Western blot, histological studies, immunohistochemistry, and transmission electron microscopy. Our results showed that MSC-exos administration decreased collagen deposition, apoptosis, and inflammation. Exosomes modulate the Nrf2/Keap1/p62 pathway, restoring autophagy and Nrf2 levels through modulation of the non-canonical pathway of Nrf2/Keap1/p62. Additionally, MSC-exos regulated miR-153-3p, miR-27a, miR-144 and miRNA-34a expression. In conclusion, the present study shed light on MSC-exos as a cytoprotective agent against EMT and tumorigenesis in chronic liver inflammation.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.