The role of intestinal mucosa oxidative stress in gut barrier dysfunction of severe acute pancreatitis

BACKGROUND : Severe acute pan - creatitis (SAP) is a serious s ystemic disease with a sustained high mortality rate. Extensive evidence has shown that gut barrier dysfunc - tion plays a critical role in the pathophysiology of SAP . AIM: Investigating the role of intestinal mucosa oxidative stress in gut barrier dysfunction of SAP. MATERIALS AND METHODS: Twenty-four BALB/c mice were randomly divided into two groups with twelve mice each group. The SAP group mice received six intraperitoneal injec - tions of cerulein (50 µg/kg) at 1-hour intervals, then given one intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS from E. coli ) for inducing SAP. Normal saline was given to the mice of control group. The animals of each group were averaged to two batches. Four and eight hours after the final injection, respectively, mice were anesthetized and blood and tissue samples were harvested for examination. The pathological changes of pancreas and gut were observed and scored. The serum levels of di - amine oxidase (DAO), amylase and tumor necro - sis factor-alpha (TNF- α) were measured. The contents of malondialdehyde (MDA) and reduced glutathione (GSH) and activity of superoxide dis - mutase (SOD) and xanthine oxidase (XO) in gut mucosa were detected. In gut mucosa, the cas - pase-3 activity was measured and the cell apop - tosis and apoptosis index (AI) were determined by terminal deoxynucleotidyl transferase-mediat - ed dUTP nick end labeling (TUNEL) assay. The data were analyzed by ANOVA and t-test. RESULTS: At four and eight hours after SAP in - duction, the SAP group mice had significantly higher pancreatic and gut pathological scores ( p < 0.01) and increased serum levels of amylase ( p < 0.05), DAO and TNF- α (p < 0.01 ) and increased MDA contents and XO activity of gut mucosa ( p < 0.01) compared with those of control mice. There were significantly lower GSH contents ( p < 0.05) and SOD activity ( p < 0.01) of gut mucosa in the SAP mice. It was also observed that the gut mu - cosa cells of SAP mice had significantly higher caspase-3 activity and apoptosis index ( p < 0.01). CONCLUSIONS: In SAP, waterfall-style re - lease of inflammatory factors such as TNF- α led to ischemia-reperfusion injury of gut mu - cosa which resulted in serious oxidative stress and activation of caspase-3 pathway and se - vere apoptosis of gut mucosa. Therefore, in - testinal mucosal oxidative stress may play an important role in the mechanism of gut barrier dysfunction.