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

Xiaochun Xie; Chenchen Yuan; Ling Yin; Qingtian Zhu; Nan Ma; Weiwei Chen; Yanbing Ding; Weiming Xiao; Weijuan Gong; Guotao Lu; Zhenglei Xu; Weiqin Li

doi:10.1016/j.bbrc.2019.09.125

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. Epub 2019 Oct 3.

Authors

Xiaochun Xie¹, Chenchen Yuan², Ling Yin³, Qingtian Zhu³, Nan Ma², Weiwei Chen⁴, Yanbing Ding³, Weiming Xiao³, Weijuan Gong⁵, Guotao Lu⁶, Zhenglei Xu⁷, Weiqin Li⁸

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acinar Cells / cytology*
Acinar Cells / drug effects
Amylases / blood
Animals
Aporphines / pharmacology*
Cell Survival
Disease Models, Animal
Down-Regulation
Lipase / blood
Male
Mice
Mice, Inbred ICR
Necrosis / prevention & control*
Pancreas / metabolism
Pancreatitis / chemically induced
Pancreatitis / prevention & control*
Pancreatitis, Acute Necrotizing / chemically induced
Protein Kinases / metabolism
Quinolines / pharmacology*
Reactive Oxygen Species
Receptor-Interacting Protein Serine-Threonine Kinases / metabolism

Substances

2,7-dioxo-2,7-dihydro-3H-naphtho(1,2,3-de)quinoline-1-carboxylate
Aporphines
Quinolines
Reactive Oxygen Species
MLKL protein, mouse
Protein Kinases
Receptor-Interacting Protein Serine-Threonine Kinases
Ripk3 protein, mouse
Lipase
Amylases