The Effects And Possible Involved Mechanisms Of Glutamine On Intestinal Barrier In Rats Model With Severe Acute Pancreatitis

Objective: To explore the effects and possible mechanisms of glutamine in rats with severe acute pancreatitis.Methods: 72 SD rats were randomly divided into severe acute pancreatitis 3h, 6h, 12h groups(SAP ,N=8), sham operation 3h, 6h, 12h group(Sham, N=8), glutamine treatment 3h, 6h,12h groups(SAP-G, N=8). Retrograde pancreatic ductal injection of 5% cholate in rats was used to establish SAP models. Sham operation model was induced by opening the abdominal cavity without injection and then the abdomen was closed. In treated group, glutamine(1ml/100g) was given by enema half hour before inducing SAP model. Animals were sacrificed at the time points 3h, 6h, 12h after operation. Pancreatic injury was evaluated, the serum or plasma levels of TNF-α, DAO and endotoxin were detected; Western Blotting was used to determine the expressions of the tight junction protein occludin in the intestinal mucosal endothelial cells at the time points of 3h, 6h, 12h after operation. The ultrastructural changes of the ileum at the time point of 6h after operation was observed.Results: (1) The Pancreatic lobules of Sham were arranged regularly and normal pancreatic cells in the light microscope. In the SAP group, it can be seen of inflammatory cell infiltrate, hemorrhage, necrosis in pancreatic tissue, but the lower in the treat group compared with that of in SAP group. (2) The serum diamine oxidase, plasma TNF-αand endotoxin levels in SAP group began to increase at 3 hours later after operation, reache the peak at 6 hours later, decline at 12 hours later.The level of TNF-αin SAP group and the glutamine enema group were much higher(p<0.01) than that in the sham group, but the level of these parameters in glutamine enema group were lower than that in SAP group (p<0.01). The blood plasma or serum concentration of DAO and endotoxin in SAP group were significantly higher than that in the Sham group. While, in glutamine pretreated group they were higher than those in Sham group (p<0.01), but were lower than those in SAP group (p<0.01). (3) It can be found the structural integrity of intestinal mucosa in the Sham group with electron microscope. The height of the villi in Sham group were significant higher than that in the glutamine pretreated group and SAP group (p<0.01). (4) The occludin protein expressions in SAP group were the lowest in three groups, glutamine pretreated group were higher than that in the SAP group (p<0.05), but lower than that in the Sham group (p<0.05).Conclusions: Glutamine treatment reduces the serum DAO level,improves endotoxemia, and significantly alleviates the pathological injury of the pancreas. The protective mechanisms of glutamine for SAP may involve reducing the plasma levels of TNF-α, enhancing intestinal cell tight junction protein Occludin expression in rats.