Role of JAK2-STAT3 signaling pathway in pancreatic injury and systematic inflammatory response in rats with acute necrotizing pancreatitis

Abstract

Objective \nTo investigate the function of JAK2-STAT3 signaling pathway in pancreatic injury and systematic inflammatory response in rats with acute necrotizing pancreatitis (ANP). \n \n \nMethods \nSD rats were randomly divided into the ANP group (n=48), ANP+ JAK2 inhibitor Ruxolitinib group (ANP+ R group, n=48), ANP+ STAT3 inhibitot Stattic group (ANP+ S group, n=48), ANP+ Ruxolitinib+ Stattic group (ANP+ R+ S group, n=48), and sham operation group (SO group, n=48). 5% sodium taurocholate injection via retrograde pancreatobiliary duct was used to establish ANP model. Blood samples from abdominal aorta and pancreatic tissue were collected after 3 h, 6 h, 12 h and 18 h after modeling. Serum amylase (AMY) and tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) were tested. JAK2 and STAT3 mRNA expression and protein expression of p-JAK2 and p-STAT3 in pancreas were examined by RT qPCR and western blot, respectively. \n \n \nResults \nAMY, TNF-α and IL-4 in plasma, and JAK2 mRNA, STAT3 mRNA, p-JAK2 protein and p-STAT3 protein at different time points in ANP group were all obviously higher than those in SO group(P<0.05). Serum AMY, TNF-α and IL-4 in ANP+ R group, ANP+ S group and ANP+ R+ S group at different time points were lower than those in ANP group [12 h (5 391±1 009), (6 130±1 227), (4 818±992)U/L vs (8 524±1 360) U/L; (147.25±27.85), (156.25±23.17), (127.87±21.39)ng/L vs (187.58±20.09)ng/L; (45.89±16.95), (50.19±15.87), (38.87±14.03)ng/L vs (58.85±9.34)ng/L]. JAK2 mRNA and p-JAK2 protein, STAT3 mRNA and p-STAT3 protein in ANP+ R group and ANP+ R+ S group at different time points were obviously lower than those in ANP group (12 h0.357±0.091 vs 0.597±0.121, 1.115±0.203 vs 1.217±0.213, 0.361±0.089 vs 0.489±0.097, 0.965±0.189 vs 1.128±0.217, 0.362±0.092 vs 0.597±0.121, 1.107±0.212 vs 1.217±0.213, 0.297±0.087 vs 0.489±0.097, 0.713±0.184 vs 1.128±0.217). STAT3 mRNA and p-STAT3 protein in ANP+ S group were obviously lower than those in ANP group(0.319±0.107 vs 0.489±0.097, 0.849±0.177 vs 1.128±0.217), and the difference was statistically different (P<0.05). \n \n \nConclusions \nThe activation of JAK2-STAT3 signaling pathway in pancreas may play a key role in the pathogenesis of systematic inflammatory response in ANP. \n \n \nKey words: \nPancreatitis, acute necrotizing;\xa0Janus kinase 2;\xa0STAT3 transcription factor