Effects of peroxisome proliferator-activated receptors-γ ligand on hyperlipidemic rats with severe acute pancreatitis

Abstract

Objective To explore the effects of rosiglitazone (ROSI),a PPAR-γ ligand,on hyperlipidemia with severe acute pancreatitis (SAP) in the rat model induced by sodium taurocholate injected into intra-bile-pancreatic duct and explore their underlying mechanism.Methods A total of 120 male SD rats were randomly divided into two groups,and eighty rats were fed with high fat diet for two weeks to induce experimental hyperlipemia and the rest received normal diet.The rats fed with normal diet were divided into two groups:sham operation group (SO group,n =20) and SAP group (n =20).The hyperlipidemic rats were randomly divided into four groups:sham operation hyperlipidemia rats group (HL group,n =20),hyperlipidemia with acute pancreatitis group (HAP group,n =20),ROSI prevention group (HR group,n =20) and antagonist group (HRI group,n =20).Rats of SAP group and HAP group were induced by a retrograde infusion of 5％ sodium tauroholate into bile-pancreatic duct,whereas the rats in SO group and HL group were induced by saline instead; rats in HR group were administered ROSI (10 mg/kg) intra-peritoneally 1 hour prior to sodium taurocholate; rats in HRI group were administered GW9662 (0.3 mg/kg) intraperitoneally 30 min prior to ROSI.Rats from each group were sacrificed by exsanguination 12 h after the induction of pancreatitis.Blood samples were taken from all animals to measure serum amylase (AMY),total cholesterol (TC),triglycerides (TG).The severity of pancreatitis was evaluated by histological score of pancreatic injury.The level of nuclear factor (NF)-KB p65 protein in pancreas was measured by immunohistochemistry.The levels of intercellular adhesion molecule (ICAM-1) protein and tumor necrosisfactor-α (TNF-α) protein were detected by using Western blot analysis.Results The serum levels of TC and TG in HL group and HAP group were significantly higher than those in SO group and SAP group (10.86 ± 1.47,10.42±0.95vs.1.72±0.13; 1.24±0.28,1.36±0.13 vs.0.61 ±0.12,0.54±0.08; all P＜ O.05).Compared with SAP group,the levels of serum AMY,the pancreas pathological score,the levels of NF-KB p65,ICAM-1 and TNF-α in pancreas in the HAP group were significantly higher in HAP group (P ＜ 0.05).Compared with the HAP group and HRI group,HR group significantly decreased the levels of serum AMY,TC and TG; pancreas pathological score; the levels of NF-KB p65,ICAM-1 and TNF-α in pancreas significantly decreased in HR group (2006.9 ± 331.9 vs.6501.9 ± 3771.0,5892.2 ± 474.3 ; 4.36 ± 0.99 vs.10.42 ±0.95,11.08 ± 1.05; 0.58 ±0.12 vs.1.36 ±0.13,1.58 ±0.12; all P ＜0.05),but there were no statistically significant differences in those biomarkers between HAP group and HRI (P ＞ 0.05).Conclusions Our study demonstrated that hyperlipidemia aggravated the severity of sodium taurocholateinduced severe acute pancreatitis and ROSI exerted anti-hyperlipidemic effect and anti-inflanmatory effect against hyperlipidemia rats with sodium taurocholate-induced severe acute pancreatitis. Key words: Peroxisomeproliferator-activated receptors-γ; Rosiglitazone ; Severe acute pancreatitis; Cytokine