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

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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.

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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

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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.

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Author notes

  1. Liang Xia and Nonghua Lu equal contribution by the corresponding authors.

Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, People’s Republic of China

    Jianhua Wan, Jie Chen, Dangyan Wu, Xiaoyu Yang, Yaobin Ouyang, Yin Zhu, Liang Xia & Nonghua Lu

Authors
  1. Jianhua Wan
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  2. Jie Chen
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  3. Dangyan Wu
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  4. Xiaoyu Yang
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  6. Yin Zhu
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  7. Liang Xia
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Contributions

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.

Corresponding authors

Correspondence to Liang Xia or Nonghua Lu.

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Conflict of interest

The authors declare that there are no conflicts of interest.

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Wan, J., Chen, J., Wu, D. et al. Regulation of Autophagy Affects the Prognosis of Mice with Severe Acute Pancreatitis. Dig Dis Sci 63, 2639–2650 (2018). https://doi.org/10.1007/s10620-018-5053-0

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  • DOI: https://doi.org/10.1007/s10620-018-5053-0

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