Abstract
Objective : Severe thickening of peritoneum with vasculopathy is a characteristic finding in longterm peritoneal dialysis patients. The mechanism underlying peritoneal fibrosis and methods of prevention remain unclear. Erythropoietin (Epo) used for renal anemia may attenuate interstitial fibrosis via the inhibition of transforming growth factor-β1 (TGF-β1) in a mouse model of obstructed kidney. In the present study, we examined the effects of Epo in an experimental animal model of peritoneal fibrosis induced by chlorhexidine gluconate (CG) injection.
Materials and Methods : Sprague-Dawley rats at 8 weeks of age were used. The rats were intraperitoneally administered CG and Epo (CG+Epo group), CG alone (CG group), Epo alone (Epo group) for 28 days. A control group was also established. Expressions of hypoxia-inducible factor-1α (HIF-1α), erythropoietin receptor (Epo R), and pimonidazole were evaluated by immunohistochemistry. HIF-1α, TGF-β1 and connective tissue growth factor (CTGF) were also examined by real-time PCR.
Results : Peritoneal fibrosis developed in the CG group and it was suppressed by Epo administration. Hypoxic cells, expressing Epo R, HIF-1α or pimonidazole positive cells in the submesothelial compact zone, were observed in the CG and CG + Epo group. In the CG group, these cells were more numerous than those in the CG +Epo group. Hematocrit in the CG +Epo group was significantly higher than that in the CG group. The expressions of HIF-1α, TGF-β1 and CTGF mRNA markedly increased in the CG group, although those were reduced in the CG + Epo group.
Conclusion : In the present study, we demonstrated that repeated CG exposures resulted in peritoneal hypoxia. Epo may play an important role in ameliorating peritoneal fibrosis via improvement of hypoxia and decreasing CTGF production by inhibition of TGF-β1 expression in CG-induced peritoneal sclerosis rat models.
