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

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.