Activation Of The AMPK Pathway By AICAR Attenuates Injury In Hyperlipidemic Acute Pancreatitis Xuewen Xie (Surgery)

Objective: To explore the expression levels of adenylate-activated protein kinase(AMPK)in hyperlipidemia(HL),acute pancreatitis(AP),and hyperlipidemic acute pancreatitis(HLAP);to investigate the therapeutic effect of 5-aminoimidazole-4-carboxamide nucleotide(AICAR)in attenuating pancreatic injury in HLAP,and to elucidate AMPK mechanism of action in HLAP,targeting AMPK targets as a new entry point for the treatment of HLAP.Methods: Divide 35 healthy and clean SD male rats into 7 groups by random number table,which are control group,HLgroup,AP group,HLAP group,A+HL group,A+AP group,A+HLAP group.The animal models of HL,AP and HLAP were established by intraperitoneal injection of P407 and 20% L-arginine.The A+HL,A+AP and A+HLAP groups were injected intraperitoneally with AICAR 30 min before the administration of the model,and the rats were executed 24 h later,and serum and pancreatic tissues were collected.HE staining was performed to observe the pathological damage to the pancreas in each group,and the levels of serum triglyceride(TG),total cholesterol(CHO),amylase(AMY),lipase(LPS),alanine transaminase(ALT)and glutathione transaminase(AST)were measured in each group of rats,and glutathione aminotransferase(AST)levels;and serum malondialdehyde(MDA),superoxide dismutase(SOD)and myeloperoxidase(MPO)levels in each group;ELISA to detect serum levels of IL-1β,IL-6,IL-10 and TNF-α inflammatory factors The expression of AMPK/NF-κB in pancreatic tissue was detected by WB;TUNEL method detects pancreatic acinar cell apoptosis.Results: Compared with the control group,the pancreatic pathological score,AMY,LPS,pancreatic apoptosis,MDA,MPO,IL-1β,IL-6,TNF-α were significantly increased(P<0.05)and the levels of IL-10 and SOD were significantly reduced(P<0.05)in rats of AP group and HLAP group;compared with the control group,the levels of TG,CHO,ALT,and AST levels were significantly increased;Compared with the HL group,AP group,and HLAP group,A+HL group,A+AP group,A+HLAP grouprat pancreatic pathology score,AMY,LPS,TG,CHO,ALT,AST,pancreatic cell apoptosis,MDA,MPO,IL-1β,IL-6,TNF-α significantly lower(P<0.05),and the levels of IL-10 and SOD increased(P<0.05);pAMPK levels were signifi-cantly downregulated in the HL,AP and HLAP groups compared with the control group,while the protein levels of p-NF-κB were significantly upregulated(P<0.05);the protein levels of p-AMPK were significantly increased in the A+HL,A+AP and A+HLAP groups(P< 0.05),and the protein levels of p-NF-κB protein levels were reduced(P<0.05).Conclusion: The expression of AMPK in HLAP is significantly inhibited;AICAR can reduce the serum TG level of HLAP rats by activating the AMPK pathway,reduce the release of inflammatory factors,and improve the pancreatic oxidative response Stimulate and inhibit the apoptosis of pancreatic cells,thereby reducing the pancreatic damage of HLAP.