2. Academic Validation
  3. Acadesine alleviates acute pancreatitis-related lung injury by mediating the barrier protective function of pulmonary microvascular endothelial cells

Acadesine alleviates acute pancreatitis-related lung injury by mediating the barrier protective function of pulmonary microvascular endothelial cells

  • Int Immunopharmacol. 2022 Oct;111:109165. doi: 10.1016/j.intimp.2022.109165.
Xiandong Zhu 1,  Feixiang Duan 2,  Yan Zhang 2,  Xiaowu Wang 1,  Yongqiang Wang 1,  Jiawei Chen 1,  Lanyu Zhang 2,  Minmin Wu 2,  Zhuo Pan 3,  Bicheng Chen 4
Affiliations

Affiliations

  • 1 Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China.
  • 2 Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China.
  • 3 Department of General Surgery, First People's Hospital Affiliated to Huzhou Normal College, No. 158, Guangchang Hou Road, Huzhou, Zhejiang Province 313000, China.
  • 4 Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China. Electronic address: bichengchen@hotmail.com.
PMID: 35987144 DOI: 10.1016/j.intimp.2022.109165
Abstract

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 effects in vitro and in vivo. Moreover, Nrf2 deficiency partially eliminated the effects of acadesine-induced antioxidant 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.

Keywords

AMPK; Acute lung injury; Acute pancreatitis; Endothelial barrier dysfunction; Nrf2; Oxidative stress.

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