| Objective To study the protective effects of pioglitazone on liver injury in rats with severe acute pancreatitis,and its possible mechanisms.Methods 72 male Sprague-Dawley rats(160-200g)were randomly allocated into four groups:sham group(group C);SAP group;pretreatment with pioglitazone group(group P1, group P2);The model of SAP was induced by the retrograde injection of 5%sodium taurocholate in the pancreatic duct,10%dimethyl sulphoxide(DMSO) was injected intraperitoneally two hours prior to sodium taurocholate(STC),but which was replaced by pioglitazone(50mg/kgP1,100mg/kgP2)in group P.Sham-operated animals was executed operation,but nothing was injected,pancreas was just flipped and striked gently a few times.Rats were killed by abdominal aorta exsanguination at 3h,6h and 12h after pancreatitis induced. Liver tissue fixed in 4% formalin was for the following experiments,which included hematoxylin and eosin staining and mucosa morphological changes under light microscopy and the activity of NF-κB and Caspase-3 was tested by immunohistochemistryI (IHC), and observed the effects of pioglitazone on them.Results 1. Liver histological pathological score under microscope:The scores were continuously increasing with time prolongation in SAP group and reached its peak in the 12h,while it was roughly normal in group C at different time points.the difference was statistically significant between the C group and SAP group at different time points,but there were no statistically different within the SAP group in different time. The score changes trend were similar with SAP in P1,P2 groups by pioglitazone with time prolongation,there were statistically different between P1,P2 groups and SAP group at 6h,12h,but there was no different within P1 or P2 groups ,as it do between P1 and P2 groups in same time.2. Immunohistochemical analysis for the activity of hepatic NF-κB P65:The NF-κB P65 Positive staining mainly located in the hepatic cell nuclear of the hepatic lobule, and it was seen in the District Department of the liver cells, bile duct cells and Kupffer cells and inflammatory cells . The expressions of NF-κB P65 protein were significantly increased after SAP induced compared with C group at 3,6,12h,while significantly decreased in the P1,P2 groups compared with SAP group at 6,12h. but there was no different within P1 or P2 groups ,as it do between P1 and P2 groups in same time.3. Immunohistochemical analysis for the activity of hepatic Caspase-3:The Caspase-3 Positive staining mainly located in the hepatic cell nuclear of the hepatic lobule, and it was seen in the District Department of the liver cells, bile duct cells and Kupffer cells. The expressions of Caspase-3 protein were significantly increased after SAP induced compared with C group at 3,6,12h,while significantly decreased in the P1,P2 groups compared with SAP group at 6,12h. but there was no different within P1 or P2 groups ,as it do between P1 and P2 groups in same time.4. The expression of Caspase-3 and NF-κB p65 were significant positive correlation with histological pathological score in the SAP group and pioglitazone groups by the Pearson correlation.Conclusions (1)The increased expression of NF-κB p65 and Caspase-3 were early performance on liver injury in rats with severe acute panereatitis,and they were significant positive correlation with hepatichistologic damage in the SAP. It may be one of the pathogenesis in liver injury with severe acute panereatitis that a key enzyme of apoptosis Caspase-3 activated by NF-κB increased hepatic injury through promoting the liver cell apoptos。(2) pioglitazone inhibited the expression of NF-κB p65 and Caspase-3 expression on liver injury in rats with severe acute panereatitis, reduced the pathological damage in the SAP.
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