The Relationship Between Endogenous Ghrelin And The Imflammatory Reation And Abnormal Metabolism Of Acute Pancreatitis

CHARPTER ONETHE DYNAMIC CHANGES OF ENDOGENOUS GHRHELIN AND THE EFFECT OF GHRP-2INTERVENTION IN ACUTE NECROTIZING PANCREATITIS RATObjective To investigate the dynamic changes of endogenous ghrelin and the effect of growth hormone releasing peptide-2(GHRP-2) pre-intervention in acute necrotizing pancreatitis (ANP) rats.Methods Ninety male SD rats were randomly divided into three groups: group control (group C)、group ANP (group A) and group GHRP-2(group G). Rats in group C received sham operation and pancreas flipping. ANP model was induced by injecting2%sodium taurocholate retrogradely into biliopancreatic duct in group A and G, while rats in group G received GHRP-2(200μg/kg) intraperitoneal injection (i.p)30minutes before inducing ANP model. Rats in group C and group A received saline i.p instead. All the rats were sacrificed at3rd、6th、12th、24th、48th hour after ANP induction. Ascites were measured and pathological changes in pancreatic tissue were observed and scored. Serum AMS was detected by substrate enzymatic assay and serum ghrelin and IL-β were determined by ELISA. The expressions of ghrelin mRNA in pancreas were evaluated by quantitative PCR.Results①With obvious necrosis in general and edema, infiltration of inflammatory cell, hemorrhage, necrosis under microscope in rats of group A and G, the pathologic scores of pancreas were significantly higher than those of group C, but there was no difference between group A and G.②The weight of ascites was less in group C than those in group A and G, which was clear and reached the peak at3rd and6th hour.③The serum AMS levels of group A and G were higher than those of group C (P<0.05or P<0.01). The peak time points of group A was6th hour, which had no difference with group G④The mean levels of ghrelin in group A and G were higher than those in group C. Except the ghrelin levels at the3rd hour of group G were higher than those of group A (593.19±265.97pg/ml vs310.82±148.64pg/ml, P<0.05), the other time points of group A and G had no significant difference.⑤The levels of serum IL-1β at3rd and6th hour in group C and G were lower than those in group A (P<0.05), which reaching the peak and decreasing with time.⑥The positive correlation was found between serum ghrelin and serum IL-1β, pathologic score of pancreatic inflammatory cell infiltration.⑦The expressions of ghrelin mRNA in pancreas of group A were increased gradually with time, and were higher than those of group C at6th、12th and24th hour.Conclusions①The increasing levels of serum ghrelin in rats were positively related to serum IL-1β and pancreatic inflammatory cell infiltration.②The expressions of ghrelin mRNA in pancreas tissue were increased at early onset of ANP in rats.③The pre-interventions of GHRP-2decreased the level of serum IL-1β and increase the serum ghrelin in ANP rats, but had no effect to the pancreatic injury. CHARPTER TWOTHE RELATIONSHIP BETWEEN SERUM GHRELIN, OBESTATIN AND ABNORMAL METABOLISM OF PATIENTS WITH ACUTE PANCREATITISObjective To observe the dynamic changes of serum ghrelin, obestatin concentration in patients with acute pancreatitis(AP) and investigate their relationship with abnormal metabolism of AP.Methods The serum sample and data of clinical, biochemical tests of83patients with AP were studied on the1st,3rd,5th day after admission, contrasted with24patients without infection as control group. Serum concentration of ghrelin, obestatin was detected by the enzyme-linked immune assay (EIA). The levels of ghrelin, obestatin, biochemical tests and the incidence of hyperglycemia, hyperlipidemia, hypoproteinemia, hypocalcaemia were compared between group mild acute pancreatitis (MAP) and severe acute pancreatitis (SAP), respectively. The correlation between ghrelin, obestatin with abnormal metabolism of AP was investigated.Results①A total35cases of MAP and48cases of SAP was recruited. The total incidence of hyperglycemia, hyperlipidemia, hypoproteinemia and hypocalcaemia was56.63%,48.19%,40.96%and27.71%, respectively. Except hyperglycemia, the others were more common in SAP. The incidence of hyperlipidemia, hypoproteinemia and hypocalcaemia of patients with SAP was58.33%,54.17%and39.58%, higher than them of patients with MAP(34.29%,22.86%,11.43%, P<0.05or P<0.01).The serum albumin and calcium level in group SAP was33.95±6.62g/L and1.98±0.24mmol/L, that was lower than group MAP(37.93±4.63g/L and2.16±0.21mmol/L, P<0.01).②The level of serum ghrelin in group SAP was lower than group control (58.81±79.36pg/ml vs79.31±26.03pg/ml, P<0.05) on the1st day after admission, whereas the level of serum obestatin in group MAP (16.96±40.28pg/ml) was higher than both group control (8.87±2.21pg/ml, P<0.01) and SAP (9.81±27.25pg/ml, P<0.05).③he serum ghrelin, obestatin levels gradually increased with time after admission. The level of serum ghrelin in group MAP was higher than group SAP (P<0.05) on the5th day, whereas the level of serum obestatin in group MAP was higher than group SAP both on the1st and3rd day after admission (P<0.01).④Serum ghrelin on the5th day was higher in patients with hypoproteinemia and it was positively correlated to serum albumin(r=0.317, P<0.01), however the serum obestatin on the1st day was lower in patients with hyperlipidemia and negatively correlated to serum triglyceride(r=-0.263, P<0.05).⑤The serum ghrelin on the5th day and serum obestatin on the1st,3rd day in patients with significant hyperglycemia (FBG≥11.1mmol/L) was lower than the others with FBG<11.1mmol/L.Conclusions①The incidence of abnormal metabolism in patients with AP were successively hyperglycemia, hyperlipidemia, hypoproteinemia and hypocalcaemia and it was more common and serious in SAP.②Serum ghrelin, obestatin in AP patients gradually increased with time.③Endogenous ghrelin and obestatin is correlated to abnormal metabolism of acute pancreatitis:serum ghrelin was positively correlated to serum albumin, while serum obestatin was negatively correlated to serum triglyceride conversely. Serum ghrelin and obestatin was lower in patients with significant hyperglycemia.