Rosiglitazone, a Peroxisome Proliferator-Activated Receptor (PPAR)-gamma Agonist, Attenuates Inflammation Via NF-kappa B Inhibition in Lipopolysaccharide-Induced Peritonitis

摘要

We assessed the anti-inflammatory effect of peroxisome proliferator-activated receptor (PPAR)-gamma agonist, rosiglitazone, in a lipopolysaccharide (LPS)-induced peritonitis rat model. LPS was intraperitoneally injected into rats to establish peritonitis model. Male Sprague-Dawley (SD) rats were assigned to normal saline (the solvent of LPS), LPS, rosiglitazone plus LPS, and rosiglitazone alone. A simple peritoneal equilibrium test was performed with 20 ml 4.25 % peritoneal dialysis fluid. We measured the leukocyte count in dialysate and ultrafiltration volume. Peritoneal membrane histochemical staining was performed, and peritoneal thickness was assessed. CD40 and intercellular adhesion molecule-1 messenger RNA (ICAM-1 mRNA) levels in rat visceral peritoneum were detected by reverse transcription (RT)-PCR. IL-6 in rat peritoneal dialysis effluent was measured using enzyme-linked immunosorbent assay. The phosphorylation of NF-kappa B-p65 and I kappa B alpha was analyzed by Western blot. LPS administration resulted in increased peritoneal thickness and decreased ultrafiltration volume. Rosiglitazone pretreatment significantly decreased peritoneal thickness. In addition to CD40 and ICAM-1 mRNA expression, the IL-6, p-p65, and p-I kappa B alpha protein expressions were enhanced in LPS-administered animals. Rosiglitazone pretreatment significantly decreased ICAM-1 mRNA upregulation, secretion of IL-6 protein, and phosphorylation of NF-kappa B-p65 and I kappa B alpha without decreasing CD40 mRNA expression. Rosiglitazone has a protective effect in peritonitis, simultaneously decreasing NF-kappa B phosphorylation, suggesting that NF-kappa B signaling pathway mediated peritoneal inflammation induced by LPS. PPAR-gamma might be considered a potential therapeutic target against peritonitis.