P1205ESTABLISHMENT OF HYPOCHLORITE-INDUCED PORCINE MODEL OF PERITONEAL FIBROSIS

Abstract

Abstract Background and Aims Patients with kidney failure rely on life-saving peritoneal dialysis to facilitate waste exchange and maintain homeostasis of physical conditions. However, peritoneal dialysis often results in peritoneal fibrosis and organ adhesion that subsequently compromise the efficiency of peritoneal dialysis and normal functions of visceral organs. Despite rodent models provide clues on the pathogenesis of peritoneal fibrosis, no current large animal model which shares high degree of physiological and anatomical similarities to human is available, limiting their applications on the evaluation of pre-clinical therapeutic efficacy. Method In this study, we established for the first time, porcine model of peritoneal fibrosis by the use of a bleach-like chemical, sodium hypochlorite. We demonstrated that intraperitoneal injection of 30ml/kg B.W., 0.1%-0.2% (0.1mM-0.2mM) hypochlorite induced peritoneal fibrosis and visceral organ adhesions in 5-week-old piglets. Results A dose- and time-dependent severity of peritoneal fibrosis characterized by mesothelium fragmentation, αSMA+ myofibroblasts accumulation, organ surface thickening and type I collagen deposition were observed. We also demonstrated that hypochlorite-induced overexpression of IL1β, CX3CL1 and TGFβ on the peritoneal mesothelium mimicked the mechanism of peritoneal dialysis-induced peritoneal fibrosis in human patients. Conclusion This pig model could not only be used as a platform for studying fibrosis/scar formation, but can also be used to evaluate the efficacy of potential candidates on the prevention (e.g. compounds) and treatments (e.g. stem cells) for regenerative medicine.