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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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.
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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