2. Academic Validation
  3. NQDI-1 protects against acinar cell necrosis in three experimental mouse models of acute pancreatitis

NQDI-1 protects against acinar cell necrosis in three experimental mouse models of acute pancreatitis

  • Biochem Biophys Res Commun. 2019 Nov 26;520(1):211-217. doi: 10.1016/j.bbrc.2019.09.125.
Xiaochun Xie 1,  Chenchen Yuan 2,  Ling Yin 3,  Qingtian Zhu 3,  Nan Ma 2,  Weiwei Chen 4,  Yanbing Ding 3,  Weiming Xiao 3,  Weijuan Gong 5,  Guotao Lu 6,  Zhenglei Xu 7,  Weiqin Li 8
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China.
  • 2 Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
  • 3 Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China.
  • 4 Department of Gastroenterology, Clinical Medical College, Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China.
  • 5 Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
  • 6 Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
  • 7 Department of Gastroenterology, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, 518000, Guangdong, China. Electronic address: [email protected].
  • 8 Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China. Electronic address: [email protected].
PMID: 31587872 DOI: 10.1016/j.bbrc.2019.09.125
Abstract

NQDI-1, an inhibitor of ASK1, has been reported to have protective effects in several experimental human disease models. However, the role of NQDI-1 in acute pancreatitis (AP) has not been reported. In this study, we found that NQDI-1 could attenuate histological damage of pancreatic tissue as well as the levels of serum amylase and Lipase in a mouse model of AP induced by caerulein. Moreover, the production of Reactive Oxygen Species (ROS) and the expression of necrosis-related proteins (RIP3 and p-MLKL) were also reduced after NQDI-1 administration. Correspondingly, we elucidated the effect of NQDI-1 in vitro and found that NQDI-1 protected against pancreatic acinar cells necrosis via decreasing the ROS production and RIP3 and p-MLKL expression. In addition, we identified the protective effect of NQDI-1 on AP through two other mouse models induced by l-arginine and pancreatic duct ligation. Taken together, these findings showed that NQDI-1 could reduce the acinar cells necrosis and alleviate the severity of AP, which may afford a new therapeutic target on pancreatic necrosis in AP clinically.

Keywords

Acute pancreatitis; NQDI-1; Necrosis; Pancreatic acinar cells; Reactive oxygen species.

Figures
Products