Role Of Pioglitazone In Severe Acute Pancreatitis With Rats

Objective: To assess the role of inflammation medium in the pathogenesis oftaurocholic acid-induced severe acute pancreatitis (SAP), and to evaluate thepreventive effects of pioglitazone, a ligand of Peroxisome proliferator-activatedreceptor gamma, towards the development of acute pancreatitis, and to investigatethe pathogenesy of SAP.METHODS: Male Sprague-Dawley(SD) rats (160-200g) were randomly allocatedinto three groups(n=18 for each group): (a) SAP group. Acute pancreatitis(AP) wasinduced in male SD rats by the retrograde injection of 1ml/kg.m of 50 g/L sodiumtaurocholate (STC) in the pancreatic duct. 10% dimethyl sulphoxide (DMSO) wasinjected intraperitoneally two hours prior to STC; (b) Pioglitazone group (same asSAP group, but 10% DMSO was replaced by pioglitazone administeredintraperitoneally, 2mg/100g); (C)Sham group. Sham-operated animals served ascontrol. Operation was executed, STC was not injected, but pancreas was flippedand striked gently three times. After operation, rats were given freedom to drinkwater, but were fasted. Rats were killed by abdominal aorta exsanguination at 3, 6and 12h after the inducetion of pancreatitis. Serum and ascitic activities of amylase,ascetic capacity, the wet pancreatic weight/dry pancreatic weight ratio, histologicscore, levels of intercellular adhesion molecule-1(ICAM-1) and nuclearfactor-kappa B (NF-κB) in pancreatic tissue were measured..RESULTS: (1) Sham group displayed normal pancreatic structure both in theexocrine and endocrine. The SAP group showed diffuse focal areas of pancreatichemorrhage, necrosis and severe edema. There were obvious adipo-saponificationin many places of abdominal cavity. There were also those characteristic such aspancreatic hemorrhage, necrosis ,severe edema and adipo-saponification inpioglitazone group , but the levels of those injuries were lower than those ofSAP group;(2) The wet pancreatic weight/dry pancreatic weight ratio, asceticcapacity, serum and ascitic activities of amylase in the SAP group weresignificantly higher than those of the sham group and pioglitazone grouprespectively (P<0.01 or P<0.05); (3)According to Kusske criteria, the pancreatichistologic score showed that there existed significant difference in the SAP groupin the interstitial edema, inflammatory infiltration, parenchyma necrosis andparenchyma hommorrhage in comparison with those of the sham group andpioglitazone group respectively (P<0.01, P<0.05);(4) The expression of NF-κBand ICAM-1 in sham group was lower than those of SAP group and pioglitazonegroup(P<0.01); there were significant difference between the expression of NF-κBand ICAM-1 in SAP group and those of pioglitazone group(P<0.05 or P<0.01) at12h after after the inducetion of pancreatitis.Conclusions:①The pretreatment of pioglitazone could degrade serum and asciticactivities of amylase , weight/dry pancreatic weight ratio, ascetic capacity andhistologic score, which show that pioglitazone is ability to reduce acutepancreatitis in rat. ②NF-κB and ICAM-1 were expressed significantly in SAPgroup, but the pretreatment of pioglitazone could inhibit the activation of NF-κBand ICAM-1 in pancreas, mitigate pancreatic injury, and there was the positivecorrelation between histologic score and expressions of NF-κB and ICAM-1,whichsuggest that pioglitazone educe the effect of anti-inflammatory by NF-κB way.③we thought that pioglitazone had some beneficial effects on the development ofsevere acute pancreatitis.