Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 111, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2022.109165
Keywords
Acute pancreatitis; Acute lung injury; AMPK; Nrf(2); Oxidative stress; Endothelial barrier dysfunction
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Funding
- National Natural Sci-ences Foundation of China [81572087]
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This study discovered that acadesine can alleviate inflammation and tissue damage in SAP-ALI by modulating the Nrf2-dependent antioxidant pathway through activating AMPK. These findings are of great significance for the treatment of SAP-related lung injury.
Severe acute pancreatitis (SAP) is a condition characterized by highly fatal acute inflammation and is usually associated with multiple organ dysfunction syndrome. Acute lung injury (ALI) is the most common complications of SAP, which is the accelerator of other organ dysfunction caused by SAP and the primary cause of early death due to SAP. Acadesine, an adenosine analog and an AMPK activator, has been discovered to modulate glucose and lipid metabolism, and inhibit the production of pro-inflammatory cytokines and iNOS. However, its role in SAP-ALI and its mechanism remains unclear and need to be explored. Herein, we discovered that acadesine mitigated the generation of reactive oxygen species (ROS) in human pulmonary microvascular endothelial cells (HPMECs), alleviated apoptosis and recovered barrier integrity, thereby contributing to anti-inflammatory ef-fects in vitro and in vivo. Moreover, Nrf2 deficiency partially eliminated the effects of acadesine-induced anti-oxidant effects and thus weakened the protective effects on cells and Nrf2-knockout (Nrf2(-/-)) mice. This study demonstrates that acadesine attenuated SAP-ALI associated inflammation and tissue damage by modulating the Nrf2-dependent antioxidant pathway by triggering AMPK. These findings are of great significance for the treatment of SAP-related lung injury.
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