Maresin-1 Inhibits Oxidative Stress and Inflammation and Promotes Apoptosis in a Mouse Model of Caerulein-Induced Acute Pancreatitis
Chengjie Lv, Qi Jin
Department of Neonatal Surgery, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland)
Med Sci Monit 2019; 25:8181-8189
This study aimed to investigate the effects of maresin-1 (MaR1) in a mouse model of caerulein-induced acute pancreatitis (AP).
MATERIAL AND METHODS: Fifty C57BL/6 mice with caerulein-induced AP were divided into the untreated control group (N=10), the untreated AP model group (N=10), the MaR1-treated (low-dose, 0.1 Î¼g) AP model group (N=10), the MaR1-treated (middle-dose, 0.5 Î¼g) AP model group (N=10), and the MaR1-treated (high-dose, 1 Î¼g) AP model group (N=10). Enzyme-linked immunoassay (ELISA) measured serum levels of amylase, lipase, tumor necrosis factor-alpha (TNF-Î±), interleukin-1Î² (IL-1Î²), and IL-6 and mRNA was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Malondialdehyde (MDA), protein carbonyls, superoxide dismutase (SOD), and the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) were measured. Histology of the pancreas included measurement of acinar cell apoptosis using the terminal-deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) assay. Western blot measured Toll-like receptor 4 (TLR4), MyD88, and phospho-NF-ÎºB p65, and apoptosis-associated proteins Bcl-2, Bax, cleaved caspase-3, and cleaved caspase-9.
RESULTS: Following treatment with MaR1, serum levels of amylase, lipase, TNF-Î±, IL-1Î², and IL-6 decreased, MDA and protein carbonyl levels decreased, SOD and the GSH/GSSG ratio increased in a dose-dependent manner. In the MaR1-treated AP mice, inflammation of the pancreas and the expression of inflammatory cytokines, pancreatic acinar cell apoptosis, Bcl-2 expression, and expression of TLR4, MyD88, and p-NF-ÎºB p65 were reduced, but Bax, cleaved caspase-3, and cleaved caspase-9 expression increased.
CONCLUSIONS: In a mouse model of caerulein-induced AP, treatment with MaR1 reduced oxidative stress and inflammation and reduced apoptosis.
Keywords: Apoptosis, Inflammation, Pancreatitis