The Roles Of Ghrelin In Acute Necrotizing Pancreatitis Associated Acute Gastric Mucosal Lesion

Objective To investigate the roles of ghrelin in acute necrotizing pancreatitis associated acute gastric mucosal lesion in rats, and to assess the effect of antioxidant melatonin on ghrelin in gastric mucosa.Methods Seventy-two SD rats were randomly divided into control group (group C, n=24), ANP group (group A, n=24) and melatonin intervention group (group M, n=24). In group A, SD rats were injected three times intraperitoneally with 6% L-Arginine (3×1.5 g/kg) in an interval of 1 hour for ANP. In group C, SD rats received the same amount of saline at the same time. In group M, melatonin (50μg/kg) was administered intraperitoneally 0.5 hour before L-Arginine injection. Rats were killed at 6,12,24 hours after the last intraperitoneal injection. The pathologic changes of pancreatic tissue and were observed under microscopes, serum amylases were measured and the concentrations of serum ghrelin and IL-6 were detected by ELISA. Ghrelin mRNA and NF-κB p65 mRNA in gastric tissue were determined by RT-PCR, and NF-κB p65 protein in gastric tissue at 24 h point was determined by Western Blot. The levels of MDA and MPO in gastric mucosal of each group were assayed, also the T-SOD activity.Results In group A, the pathologic changes of pancreatic tissue and gastric tissue, serum amylases and serum ghrelin and IL-6 levels were significantly higher than those in group C (P<0.05); in group M, those were significantly lower than those in group A (P<0.05), but still higher than those in group C (P <0.05). Ghrelin mRNA was decreased, NF-κB p65 mRNA and its protein expression were increased in gastric tissue in group A as time gone on, the changes were milder in group M (P<0.05). In group A, the levels of MDA and MPO in gastric tissue were higher than those in group C (P<0.05), but they were reduced in group M (P<0.05). The activity of T-SOD was down-regulated in group A, and reduced in group M (P<0.05).Conclusion (1) Down-regulation of ghrelin in gastric tissue is probably one player, which enhance the expression of NF-κB p65 increasing in ANP associated AGML and it may be involved to against the oxidative stress injury and neutrophilic granulocyte infiltrating; (2) Ghrelin is up-regulated in gastric tissue as a self-protective factor which activated by melatonin, it would exhibite anti-inflammatory action and antioxidation with melatonin ANP associated AGML.