关键词: 磷酸腺苷活化蛋白激酶(AMPK), 5-氨基-4-咪唑羧基酰胺核苷(AICAR), 氧化应激, 重症急性胰腺炎(SAP)

Abstract: Objective To investigate the protective effect of AMPK activator AICAR on pancreatic injury in rats with severe acute pancreatitis (SAP) by inhibiting inflammatory and oxidative stress. Methods The rats were randomly divided into three groups with 6 in each as follows: sham operation group(NC group),model group(SAP group)and experimental group[(SAP+AICAR) group, given AICAR 400 mg/kg intervention 2 h before modeling]. 5% sodium bezoar cholic acid was pumped into the bile duct with a dosage of 0.1 mL/kg for modeling. The rats were anesthetized with isoflurane 24 hours after modeling, and 5-7 mL of blood from the abdominal aorta was collected, and the heart was cut off for euthanasia.The ratio of p-AMPK/AMPK was determined by Western blot to determine AMPK activation; Pathological injury and edema of pancreas were observed by HE staining; The expressions of monocyte chemotaxis protein 1(MCP-1) and the myeloper-oxidase(MPO) positive cells were counted with immunohistochemical staining; The contents of amylase,lipase,IL-6 and TNF-α in serum were determined by ELISA. The content of malondialdehyde (MDA) and the activity of super-oxide dismutase (SOD) in pancreatic tissues were determined. Results The level of pancreatic phosphorylated AMPK in SAP group was significantly lower than that in NC group (P＜0.05), and the level of pancreatic phosphorylated AMPK in experimental group was significantly higher than that in SAP group (P＜0.01).The pathological score and pancreatic moisture content of the SAP group were significantly higher than those of the NC group (P＜0.05), and the pathological score and pancreatic moisture content of the experimental group were significantly lower than those of the SAP group (P＜0.01).The expression of MCP-1, the number of MPO positive cells, the contents of amylase,lipase,IL-6 and TNF-α in serum, the content of MDA and the activity of SOD in pancreatic tissue in SAP group were significantly higher than those in NC group(P＜0.05).The expression of MCP-1, the counting of MPO positive cells, the contents of amylase,lipase,IL-6 and TNF-α in serum, the content of MDA and the activity of SOD in pancreatic tissue in experimental group were significantly lower than those in SAP group (P＜0.01). Conclusions AMPK activator inhibites inflammatory and oxidative stress responses in SAP rats and alleviates pancreatic injury as well as pancreatic edema.

Key words: adenosine monophosphate activated protein kinase(AMPK), 5-amino-4-imidazolecarboxamide riboside (AICAR), oxidative stress, severe acute pancreatitis (SAP)