The Expression And Significance Of TAP And HMGB1 In Rats With Acute Pancreatitis

Objective:To research the relationship in expression of the early inflam-matory factor trypsinogen activation peptide(TAP) and the late inflammatory cytokines high mobility group box 1(HMGBl), and the inhibitory effect of ethyl pyruvate on HMGB1 in rats with acute pancreatitis(AP). Methods:The 184 Spragye-Dawley rats were randomly divided into three groups:control group (A group, n=8), model group (B group, n=96), ethyl pyruvate(EP) treatment group (C group, n=80); AP Models of B,C groups were each divided into light (MAP sub-group) and heavy (SAP sub-group) two levels. Severe acute pancreatitis was induced by retrograde injection of 5%sodium taucrocholate into the biliopancreatic duct, with 2%sodium taucrocholate to induce mild acute pancreatitis in Group B and Group C. Group C received EP solution (28mmol/L, 40mg/Kg-6h) by tail vein beginning 2,8,14,20,26,32,38 and 44 hours after induction of AP, while Group B rats received the same amount of ringer lactate solution balance as a placebo. The samples of blood and pancreas were collected directly to detect TAP and HMGB1 levels in group A. After 1,3,6,12,24 and 48 hours, blood and pancreas were collected for TAP, HMGB1 mRNA and protein determinations. The concentrations of TAP were measured by enzyme-linked immunosorbent assay (ELISA), meanwhile, RT-PCR to test mRNA content of HMGB1 and Western Blot analysis its protein expression. A point scoring system histologic features was respectively used to evaluate the severity of pancreatitis, with correlation analyse in TAP and HMGB1. And correlations in each two of TAP, HMGB1 and pancreatic histopathological score. Results:TAP concentration began to increase at 1h after molding, reached the peak at 3h-6h, decreased to normal at 24h; HMGB1 upregulated at 12h, reached the peak at 24h, maintained a high expression at 48h. Compared with Group A, the TAP level and pancreatic histological score were higher in Group B and C, and the SAP models were obviously to the MAP models (P<0.01, respectively). HMGB1 expression was significantly increased in Group B and Group C compared with Group A (P<0.05, respectively), and it significantly decreased HMGB1 concentration in serum and pancreas of Group C from 12 hours after induction of AP compared to Group B (P<0.05, respectively), with the SAP sub-group increased mucher than MAP sub-group at the same point (P<0.05, respectively). Correlation coefficient of TAP and pancreatic histological score was r=0.863, with r=0.847 of HMGB1 and pancreatic histological score. Correlation coefficient of TAP and HMGB1 in MAP and SAP were r=0.518 and r=0.557 separately (P<0.01, respectively). Conclusion:The level of TAP increased at early period and fell in the mid, with HMGB1 expression increased in the mid and stayed at a high level in the late. The increased levels of TAP and HMGB1 were positive correlated to the severity of AP, and TAP were significantly related to HMGB1, therefore TAP and HMGB1 acted important in AP. Treatment of ethyl pyruvate has a therapeutic effect on AP, with inhibitting HMGB1 expression, and reducing pancreatic injury.