Rosiglitazone Attenuates Hyperlipidemic Rats With Severe Acute Pancreatitis And Pancreatitis-associated Lung Injury

Part1. Hyperlipidemia and hyperlipidemic severe acute pancreatitis creation appreciation animal modelObjective:Through the establishment of hyperlipidemia with hyperlipidemia severe acute pancreatitis model research creation appreciation animal model。Methods:forty SD rats were randomized into four groups:normal groups(SO), hyperlipidemia groups(HL) hyperlipidemia severe acute pancreatitis groups(HAP) and severe acute pancreatitis groups (SAP).HL group and HAP groups Rats received intragastric administration of high fat diet2weeks everyday afternoon at4oclock, which induced experimental hyperlipemia, HAP groups retrograde injection of5%sodium taurocholate (0.1mL/100g) into the pancreatic duct which induced hyperlipidemia severe acute pancreatitis.model。normal rats retrograde injection of5%sodium taurocholate (0.1mL/100g) into the pancreatic duct which induced severe acute pancreatitis (SAP) model.Results:The serum levels of TC and TG、AMY in SAP group and HAP group were significantly higher than SO group and HL group all (P<0.05); The serum levels of AMY in HAP and SAP group were significantly higher than SO group and HLgroup all (P<0.05). HL group but no conspicuous inflammation present in pancreatic tissue; the histopathologic damage of pancreas in HAP group were more serious than in SAP group., the level of TC、TG、AMY in serum and in pancreatic tissue in HAP group were significantly higher than those in SAP group,while the level of TC、TG、AMY in serum and in pancreatic tissue in HAP group were significantly lower than those in SAP group.Conclusions:A model of hyperlipemia rats with hyperlipemia severe acute pancreatitis might be developed by intragastric administration of high fat diet2weeks and retrograde injection of5%sodium taurocholate into the pancreatic duct.Hyperlipemia can aggravate the histopathologic damage of severe acute pancreatitis in rats,lipid peroxidation might play a significant role in the mechanism,which hyperlipemia could aggravate the damage of severe acute pancreatitis. Part two Experimental study of the protective effects of rosiglitazone on hyperlipidemic severe acute pancreatitisObjective:To explore the effects of rosiglitazone (ROSI), PPAR-y ligand, on hyperlipidemia with severe acute pancreatitis (SAP) in the rat model induced by sodium taurocholate and explore their underlying mechanism.Methods:A total of120male SD rats were randomLy were randomLy assigned into divided into two groups, Eighty of which were received intragastric administration of high fat diet for two weeks which induced experimental hyperlipemia, the others received normal diet. The normal rats were divided into two groups:SO group(n=20) and SAP group(n=20). The hyperlipidemic rats were randomLy divided into four groups: HL group (n=20), HAP group(n=20), HRP group(n=20) and HRGPgroup(n=20).SAP group and HAP group was induced by a retrograde infusion of5%sodium tauroholate into bile-pancreatic duct; SO group and HL group were identical to the SAP group and HAP group except that saline was injected instead of sodium taurocholate; HRP group was the same as the HAP group but rats were administered ROSI (10mg/kg) via the intraperitoneal injection1hour prior to sodium taurocholate; HRGP group as the HR group but rats were administered GW9662(0.3mg/kg) via the intraperitoneal injection30min prior to ROSI. Rats from each group were killed by exsanguination12h after the induction of pancreatitis. Blood samples were taken from all subjects to measure serum amylase (AMY), total cholesterol (TC), triglycerides (TG), The severity of pancreatitis was evaluated by histological score of pancreatic injury. The expression of nuclear factor (NF)-κB p65protein in pancreas was measured by immunohistochemistry. Intercellular adhesion molecule (ICAM-1) protein and tumor necrosis factor-a (TNF-a) protein expression were studied using Western blot analysis.Results:The serum levels of TC and TG in HL group and HAP group were significantly higher than SO group and SAP group (all P<0.05); The levels of serum AMY, pancreas pathological damage, the expression of NF-κB p65, ICAM-1and TNF-α in pancreas in the HAP group were significantly higher than SAP group (all P<0.05); Compared with the HAP group and HRGP group, HRP group significantly decreased the levels of serum AMY,TC and TG; ameliorates pancreas pathological damage; down-regulating the expression of NF-κB p65, ICAM-1and TNF-α in pancreas (all P<0.05),but compared with the HAP group, HRGP group no statistically significant in each of results (all P>0.05).Conclusions:Our study demonstrated that hyperlipidemia aggravates the severity of sodium taurocholate-induced severe acute pancreatitis and ROSI exerts antihyperlipidemic effect and anti-inflammatory effect against hyperlipidemia rats with sodium taurocholate-induced severe acute pancreatitis. Part three Experimental study of the protective effects of rosiglitazone on hyperlipidemic severe acute pancreatitis-associated lung injuryObjective:The aim of this study is to investigate the effect of rosiglitazone on adhesion molecules expression in hyperlipemia severe acute pancreatitis associated lung injury in rats.Methods:A total of120male SD rats were randomLy were randomLy assigned into divided into two groups, Eighty of which were received intragastric administration of high fat diet for two weeks which induced experimental hyperlipemia, the others received normal diet. The hyperlipidemic rats were randomLy divided into four groups: HL group (n=20), HAP group (n=20), HRP group(n=20) and HRGPgroup(n=20). HAP group was induced by a retrograde infusion of5%sodium tauroholate into bile-pancreatic duct; HL group were identical to the and HAP group except that saline was injected instead of sodium taurocholate; HRP group was the same as the HAP group but rats were administered ROSI (10mg/kg) via the intraperitoneal injection1hour prior to sodium taurocholate; HRGP group as the HRP group but rats were administered GW9662(0.3mg/kg) via the intraperitoneal injection30min prior to ROSI. Rats from each group were killed by exsanguination12h after the induction of lung tissues. Blood samples were taken from all subjects to measure serum amylase (AMY), total cholesterol (TC), triglycerides (TG), The severity of lung tissues was evaluated by histological score of lung injury. The expression of nuclear factor (NF)-κB p65protein in lung was measured by immunohistochemistry. Intercellular adhesion molecule (ICAM-1) protein and tumor necrosis factor-a (TNF-a) protein expression were studied using Western blot analysis.Results:the expression of NF-κB p65, ICAM-1and TNF-a in lung tissues. in the HAP group were significantly higher than SAP group all (P<0.05); Compared with the HAP group and HRGP group, HRP group significantly decreased the levels of serum AMY,TC and TG; ameliorates lung tissues pathological damage; down-regulating the expression of NF-κB p65, ICAM-1and TNF-a in lung tissues all (P<0.05),but compared with the HAP group, HRGP group no statistically significant in each of results all (P>0.05).Conclusions:Our study demonstrated that hyperlipidemia aggravates the severity of sodium taurocholate-induced hyperlipidemia severe acute pancreatitis and ROSI exerts antihyperlipidemic effect and anti-inflammatory effect against hyperlipidemia rats with sodium taurocholate-induced hyperlipidemia severe acute pancreatitis.