Effects of rosiglitazone on hyperlipidemic rats with severe acute pancreatitis secondary to lung injury

Abstract

Objective To explore the effects of rosiglitazone (ROSI), a peroxisome proliferator-activated receptors-gamma (PPAR-γ) ligand, on hyperlipidemia in rats with severe acute pancreatitis (SAP) associated with lung injury. Methods A total of 120 male SD rats received intragastric administration of high fat diet for two weeks to induce experimental hyperlipemia. The hyperlipidemic rats were randomly(random number) divided into six groups: hyperlipidemia (HL) group (n=20), hyperlipidemia with SAP (HP) group (n=20), hyperlipidemia with rosiglitazone intervention (HRP) group (n=20), hyperlipidemia with rosiglitazone and antagonist to rosiglitazone (HRGP) group (n=20), rosiglitazone control (HR) group (n=20) and antagonist control (HG) group (n=20). The SAP was induced by a retrograde infusion of 5%sodium tauroholate into bile-pancreatic duct, and the SAP was established in HP group, HRP group and HRGP group. In HL group, HR group and HG group, equivalent volume of normal saline was used instead of sodium taurocholate. In HRP group and HR group, ROSI (6 mg/kg) was administered via the femoral vein 1 hour prior to the administration of sodium taurocholate. In HRGP group, GW9662 (0.3 mg/kg), an antagonist to PPRA-gamma, was given via the femoral vein 30 min prior to the administration of ROSI. In HG group, only GW9662 (0.3 mg/kg) was given via the left femoral vein 30 min prior to pretend SAP modeling. Rats from each group were sacrificed by exsanguination 12 h after SAP modeling. Blood samples were taken from all subjects to measure serum amylase (AMY), total cholesterol (TC), triglycerides (TG), Successive sections of the paraffin embedded tissue from pancreas and lung were taken for pathological examination with hematoxylin-eosin (HE) staining. Histopathological changes of pancreatic and pulmonary tissues observed under light microscope were evaluated. In pulmonary tissue, nuclear factor-kappa B(NF-κB)p65 expression was assayed by immuno- histochemistry. Intercellular adhesion molecule (ICAM-1) protein and tumor necrosis factor-α (TNF-α) protein levels were studied using Western blot analysis. Results The serum levels of TC and TG in HL group and HP group were significantly higher than those in HR group and HRP group (1.24±0.28, 1.14±0.08 vs. 0.41±0.17, 0.58±0.12; 14.86±1.47, 12.42±0.96 vs. 6.52±2.04, 7.36±0.95, all P 0.05). Conclusions Our study demonstrates that ROSI exerts anti-hyperlipidemic effect and anti-inflammatory effect on hyperlipidemia in rats with sodium taurocholate-induced severe acute pancreatitis associated with lung injury by inhibiting NF-κB and down-regulating the expression of TNF-α and ICAM-1. Key words: Rosiglitazone; Hyperlipidemia; Severe acute pancreatitis; Lung injury; NF-κB