Roles Of Ghrelin In Acute Necrotizing Pancreatitis Associated With Kidney Injury

Objective To investigate the roles of endogenous ghrelin in acute necrotizing pancreatitis associated with kidney injury in rats, and to assess the effect of antioxidant melatonin on ghrelin in kidney.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, the rats were injected intraperitoneally three times with 6% L-Arginine (1. 5 g/kg) in an interval of 1 hour for ANP. In group C, the rats received the same amount of saline at the same time. In group M, 0.25% melatonin (50ug/kg) was administered intraperitoneally 0.5 hour before L-Arginine injection. Rats were killed at 6h, 12h and 24h after the last intraperitoneal injection. The pathologic changes of pancreas and kidney were observed and graded under microscope. The level of serum-amylase was detected. The level of IL-6 in serum was determined by ELISA. The expression of ghrelin mRNA and NF-κB p65 mRNA in kidney were evaluated by RT-PCR and NF-κB p65 protein in kidney at 24h time point was determined by Western Blot. The levels of MDA and MPO in kidney were assayed, also the T-SOD activity.Results In group A, the pathologic scores of the pancreas and kidney, the level of serum-amylase and IL-6 in serum 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). In group A, the expression of ghrelin mRNA in kidney was decreased, while the expression of NF-κB p65 mRNA and its protein in kidney were increased as time gone on ( P < 0. 05); in group M, those changes also appeared, but were milder than those in group A( P < 0. 05). The levels of MDA and MPO in kidney in group A were significantly higher than those in group C( P < 0. 05), but they were reduced in group M( P < 0. 05). The activity of T-SOD in kidney was down-regulated in group A, and was reduced in group M( P < 0. 05).Conclusions (1) The decreased expression of ghrelin may concerned with the level of kidney injury in acute necrotizing pancreatitis. (2) The activation of NF-κB p65, the release of oxygen free radical, and the reduction of ghrelin may be important reasons to lead to kidney injury in acute necrotizing pancreatitis. (3) Ectogenic melatonin may alleviate kidney injury by its anti-inflammatory effects and antioxidation in acute necrotizing pancreatitis, and may increase the expression of ghrelin in kidney.