Expression Of Ghrelin In Acute Necrotizing Pancreatitis In Rats With Liver Injury And The Effects Of Melatonin On It

Objective To observe the expression of ghrelin and NF-κB in acute pancreatitis in rats with liver injury, and the changes of both of them with the intervention of melatonin, to investigate the roles of ghrelin and NF-κB in this pathological process, the effects of antioxidant melatonin on ghrelin and its possible mechanism.Methods Seventy-two male SD rats were separated into 3 groups randomly: control group (group C, n=24), acute necrotizing pancreatitis group (group A, n=24), melatonin intervention group (group M, n=24). In group A, the rats were injected with 6% L-Arg(1.5g/kg) intraperitoneally at one-hour interval to induce acute necrotizing pancreatitis, 3 times totally. In group C, the rats received the same amount saline at the same time. The rats were injected with 0.25% melatonin(50μg/kg) intraperitoneally 0.5h before the first injection of L-Arg in group M. All the rats were killed at 6h,12h,24h after the third injection of L-Arg, in batches of 8. Then specimens from pancreatic and liver tissues were sliced, stained. The pathologic changes of the pancreatic and hepatic tissues were observed and graded under microscope. The arterial blood was collected and serum amylase was measured; hepatic SOD and MDA were determined after the liver tissues were homogenized. The expression of ghrelin and NF-κB mRNA were evaluated by RT-PCR while the protein NF-κB was detected by Western Blot.Results The pathologic scores of the pancreatic and hepatic tissues, serum amylase, hepatic MDA, expression of NF-κB mRNA at 6h,12h,24h and NF-κB protein at 24h of the livers in group A were significantly higher than those in group C(P< 0.05), meanwhile ghrelin mRNA and SOD of liver were lower than group C(P< 0.05). In group M, the pathologic scores of the pancreatic and hepatic tissues, serum amylase, hepatic MDA, expression of NF-κB mRNA and protein of the livers were brought down compared to those in group A(P< 0.05).Ghrelin mRNA and SOD were still lower than group C(P< 0.05).Conclusions (1) The expression of ghrelin may be related to the severity of acute pancreatitis with liver injury; NF-κB plays an important role in this pathological process;(2) Exogenous melatonin can reduce the lesions of pancreas and livers in acute necrotizing pancreatitis; it shows antioxidant and anti-inflammatory effects probably via the production of ghrelin and reduction in activity of NF-κB.