Regulation of Autophagy Affects the Prognosis of Mice with Severe Acute Pancreatitis
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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.
To explore the therapeutic effects of regulating autophagy after the onset of AP.
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.
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.
Our study found that the regulation of autophagy could alter the progression of AP induced by l-arginine or cerulein plus LPS in mice.
KeywordsAcute pancreatitis Autophagy 3-methyladenine Inflammatory
Nuclear factor κB
Microtubule-associated protein 1 light chain 3
Enzyme-linked immunosorbent assay
Sodium dodecyl sulfate
Junctional adhesion molecules
Acute lung injury
Reactive oxygen species
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.
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.
- 4.Mareninova OA, et al. Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis. J Clin Invest. 2009;11:3340–3355.Google Scholar
- 30.Wang, X. et al. Acanthopanax versus 3-Methyladenine ameliorates sodium taurocholate-induced severe acute pancreatitis by inhibiting the autophagic pathway in rats. Mediators Inflamm, 8369704 (2016).Google Scholar