Effect of adenosine inhibition of GSK-3β activity on intestinal barrier dysfunction in rats with severe acute pancreatitis

ObjectiveTo explore the protection pathway of adenosine against intestinal barrier dysfunction(IBD) in rats with severe acute pancreatitis(SAP).

MethodsA total of 64 male SD rats were randomly divided into 4 groups: sham group, adenosine treatment group(adenosine), SAP group and mPTP inhibitor cyclosporin A group.Serum amylase level and pancreatic pathology were tested to confirm the success of SAP model; the damage of small intestine tissue was observed by HE staining; the expression of P-GSK-3β in the small intestine of rats was detected by Western blotting; electronmicroscope was used to observe the changes of mitochondrial ultrastructure; differential centrifugation method was used to separate mitochondria, then, mitochondrial swelling experiments were conducted under Ca²⁺ induction.

ResultsWith the success of SAP model, the serum pancreatic amylase level was gradually increased with the extension of the time point from 0 to 12 h, which reached the peak at 12 h and decreased to the lowest at 24 h.The difference was statistically significant(P < 0.01).Staining of sections showed that SAP group had hyperemia and edema of intestinal mucosa, accompanied by necrosis of columnar epithelial cells, and even fracture and defect of some villi, while the intestinal mucosal epithelium and fluffy form of the Ade-Ⅳ group were basically complete, and the velvet arrangement was basically neat.Compared to the SAP group, the P-GSK-3β expression of the Ade-Ⅳ group increased significantly(P < 0.01).In SAP group, intestinal mitochondrial ultra-micro structure was significantly swollen, even empty bubble degeneration appeared, while in Ade-Ⅳgroup, this significantly reduced.Mitochondrial swelling experiment showed that the mitochondrial absorbance value at 520 nm was the highest in SAP group, secondary was Ade-Ⅳ group and CSA group was the lowest, and the differences were statistically significant(P < 0.01).

ConclusionsAdenosine prevents SAP intestinal barrier injury presumably by targeting the mPTP through inactivation of GSK-3β.