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Digestive Diseases and Sciences

, Volume 63, Issue 10, pp 2639–2650 | Cite as

Regulation of Autophagy Affects the Prognosis of Mice with Severe Acute Pancreatitis

  • Jianhua Wan
  • Jie Chen
  • Dangyan Wu
  • Xiaoyu Yang
  • Yaobin Ouyang
  • Yin Zhu
  • Liang Xia
  • Nonghua Lu
Original Article

Abstract

Background

Acute pancreatitis (AP) is a common inflammatory disease that may develop to severe AP (SAP), resulting in life-threatening complications. Impaired autophagic flux is a characteristic of early AP, and its accumulation could activate oxidative stress and nuclear factor κB (NF-κB) pathways, which aggravate the disease process.

Aim

To explore the therapeutic effects of regulating autophagy after the onset of AP.

Methods

In this study, intraperitoneal injections of 3-methyladenine (3-MA) and rapamycin (RAPA) in the l-arginine or cerulein plus lipopolysaccharide (LPS) Balb/C mouse model. At 24 h after the last injection, pulmonary, intestinal, renal and pancreatic tissues were analyzed.

Results

We found that 3-MA ameliorated systemic organ injury in two SAP models. 3-MA treatment impaired autophagic flux and alleviated inflammatory activation by modulating the NF-κB signaling pathway and the caspase-1-IL-1β pathway, thus decreasing the injuries to the organs and the levels of inflammatory cytokines.

Conclusion

Our study found that the regulation of autophagy could alter the progression of AP induced by l-arginine or cerulein plus LPS in mice.

Keywords

Acute pancreatitis Autophagy 3-methyladenine Inflammatory 

Abbreviations

AP

Acute pancreatitis

SAP

Severe AP

NF-κB

Nuclear factor κB

IP

Intraperitoneal

3-MA

3-methyladenine

RAPA

Rapamycin

LPS

Lipopolysaccharide

LC3-II

Microtubule-associated protein 1 light chain 3

ZO-1

Zonula occludens-1

IHC

Immunohistochemistry

LDH

Lactate dehydrogenase

ELISA

Enzyme-linked immunosorbent assay

BCA

Bicinchoninic acid

SDS

Sodium dodecyl sulfate

PVDF

Polyvinylidene fluoride

ECL

Enhanced chemiluminescence

JAM

Junctional adhesion molecules

ALI

Acute lung injury

PI3K

Phosphatidylinositol 3-kinase

ROS

Reactive oxygen species

Notes

Acknowledgments

This work was supported in part by the National Natural Science Foundation of China (No: 81460130), the Science and Technology Plan Grant (No. 20165092) from the Health Department of Jiangxi Province, China, and the Science and Technology Plan Grant (Key project) (No. GJJ160024) from the Education Department of Jiangxi Province, China.

Author’s contribution

LX and JW conceived and designed the experiments. DW, GH, YZ, YF, JW, TM, JN and GY performed the experiments. GH, XW, DW and RW analyzed the data. GH, XW and RW contributed reagents/materials/analysis tools. JW wrote the paper.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

10620_2018_5053_MOESM1_ESM.pdf (355 kb)
Supplementary material 1 (PDF 354 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of GastroenterologyThe First Affiliated Hospital of Nanchang UniversityNanchangPeople’s Republic of China

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