| Objective: To study the dynamic changes of PPARγmRNA in the pancreas of sodium taurocholic acid-induced severe acute pancreatitis (SAP), and to assess the preventive effects of pioglitazone, a ligand of Peroxisome proliferator-activated receptor gamma, on the development of STC-induced severe acute pancreatitis.METHODS: Male Sprague-Dawley(SD) rats (160-200g) were randomly allocated into five groups(n=18 for each group): (a) SAP group. Acute pancreatitis(AP) was induced in male SD rats by the retrograde injection of 1ml/kg.m of 50 g/L sodium taurocholate (STC) in the pancreatic duct. 10% dimethyl sulphoxide (DMSO) was injected intraperitoneally two hours prior to STC; (b) Pioglitazone groups (same as SAP group, but 10% DMSO was replaced by pioglitazone administered intraperitoneally, 2mg/100g,5mg/100g,10mg/100g in DMSO); (C)Sham operation group. Sham-operated animals served as control. Operation was executed, STC was not injected, but pancreas was flipped and striked gently three times. After operation, rats were given freedom to drink water, but were fasted. Rats were killed by abdominal aorta exsanguination at 3, 6 and 12h after the inducetion of pancreatitis. Serum and ascitic activities of amylase were measured .The pancreatic tissue was divided into three parts:I,Samples of pancreatic tissues for histological examination were fixed in 10% formalin and stained with hematoxylin and eosin,and histologic score was performed.II,Samples of pancreatic tissues for the wet pancreatic weight/dry pancreatic weight ratio were stored at -80℃, III, Samples of pancreatic tissues were rapidly frozen in liquid nitrogen and stored at -80℃for total RNA extraction.The concentrations of inflammatory cyctokines (TNF-α,IL-6 and IL-10) of the blood were measured by ELISA.RESULTS: (1) Sham group displayed normal pancreatic structure both in the exocrine and endocrine. The SAP group showed diffuse focal areas of pancreatic hemorrhage, necrosis and severe edema. There were obvious adipo-saponification in many places of abdominal cavity. There were also those characteristic such as pancreatic hemorrhage, necrosis ,severe edema and adipo-saponification in pioglitazone groups , but the levels of those injuries were lower than those of SAP group;(2) Pioglitazone administered(2mg/100g,5mg/100g,10mg/100g i.g.) 2 hours prior to STC,attenuated dose-dependently the pancreatic tissue damage in STC-induced pancreatitis as demonstrated by the improvement of pancreatic histology,reduce the pancreatic wet/dry pancreatic weight ratio, ascetic capacity, serum and ascitic activities of amylase , the concentrations of inflammatory cyctokines (TNF-αand IL-6) of the serum and increased serum levels of IL-10.(P<0.01 or P<0.05); (3)According to Schmidt criteria, the pancreatic histologic score showed that there existed significant difference in the SAP group in the interstitial edema, inflammatory infiltration, parenchyma necrosis and parenchyma hommorrhage in comparison with those of the sham group and pioglitazone groups respectively (P<0.01, P<0.05);(4) The expression of PPARγmRNA in sham group and SAP group was lower than those of pioglitazone groups(P<0.05); The pancreatic expression of PPARγmRNA was obviously increased in the pioglitazone groups at 3h,6h and 12h, which was dose-dependent .Conclusions:The pretreatment of pioglitazone could dose-dependent reduce acute pancreatitis in rat; Pioglitazone could activated the PPARγmRNA in pancreas pathway, mitigate pancreatic injury, which suggest that pioglitazone educe the effect of anti-inflammatory by PPARγpathway.Thus, we thought that pioglitazone had some beneficial effects on the therapy of severe acute pancreatitis in clinical situation.
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