运动预适应通过irisin-UCP2通路减轻肥胖小鼠酒精性重症急性胰腺炎OA

AIM:This study aimed to investigate the protective effect of exercise preconditioning against obe-sity-related alcoholic acute pancreatitis(OA-AP)in mice and to determine whether this protection is mediated through the irisin/UCP2 pathway.METHODS:Forty male C57BL/6 mice,aged 6 to 8 weeks,were randomly divided into four groups(n=10 per group):control(Ctrl),OA-AP model(OA-AP),exercise intervention(OA-AP+EXE),and exercise interven-tion with UCP2 inhibitor genipin(OA-AP+EXE+genipin).The OA-AP model was induced by 12 weeks of a high-fat diet combined with intraperitoneal ethanol injections.Exercise groups underwent a 12-week treadmill running protocol.Genip-in(15 mg/kg)was administered following the final ethanol injection.Samples were collected 12 hours post-modeling to evaluate histopathological injury,serum lipids levels,serum irisin level,inflammatory markers(serum amylase,IL-6,lung MPO activity),immune cell infiltration,levels of neutrophil extracellular traps(NETs)and reactive oxygen species(ROS),expression of mitochondrial function-related proteins[uncoupling protein 2(UCP2),sirtuin 3(SIRT3),peroxi-some proliferator-activated receptor γ coactivator-1α(PGC-1α),mitochondrial transcription factor A(TFAM)and heme oxygenase 1(HO-1)]in pancreatic tissue,and Fndc-5 mRNA expression in the gastrocnemius muscle.RESULTS:Com-pared with the Ctrl group,the OA-AP group showed significant increases in body weight and blood lipid levels,marked histopathological damage in pancreatic and lung tissues,elevated[serum amylase,interleukin-6(IL-6)and lung myelo-peroxidase(MPO)activity](P<0.01);increased infiltration of neutrophils and macrophages,NETs and ROS levels in pancreatic tissues(P<0.01),and decreased expression of pancreatic mitochondrial function-related proteins,serum iri-sin,and muscle Fndc-5 mRNA(P<0.01).Compared with the OA-AP group,exercise intervention significantly reduced body weight,blood lipid levels,pancreatic and lung histopathological injury,lowered the above inflammatory markers,immune cell infiltration,NETs and ROS levels(P<0.01),and increased the expression of mitochondrial function-related proteins,serum irisin,and muscle Fndc-5 mRNA(P<0.05).Administration of the UCP2 inhibitor genipin reversed these exercise-induced protective effects,with no significant differences in indicators compared to the OA-AP group(P>0.05).CONCLUSION:Exercise preconditioning alleviates OA-AP in obese mice potentially by up-regulating irisin and activat-ing the UCP2 pathway,thereby improving mitochondrial function and suppressing NETs formation and inflammatory re-sponses.