The Effect Of Rosiglitazone On Peritoneal Fibrosis Induced By Peritoneal Dialysate In Rats

ObjectiveTO investigate the effect of rosiglitazone (RGZ) in prevention of peritoneal fibrosis induced by high glucose peritoneal dialysate and erythromycin in rats.MethodsFifty SD rats were randomly divided into six groups: control group (n=5) received no treatment; normal saline group (NS group, n=9) received 20 mL normal saline plus identical voluminal solvent normal saline(2 mL per 300 g) daily intraperitoneally (IP) for 5 weeks; model group (n=9) received 20 mL 4.25% peritoneal dialysate and identical voluminal solvent normal saline(2 mL per 300 g) daily IP for 5 weeks combined with four injections of erythromycin (62.5mg on days 7, 14, 21, 28) ; dimethyl sulfoxide group (DMSO group,n=9) received 20 mL 4.25% peritoneal dialysate and identical voluminal solvent normal saline containing DMSO (2 mL per 300 g) daily IP for 5 weeks combined with four injections of erythromycin (62.5mg on days 7, 14, 21, 28); low-dose RGZ group (n=9) received 20 mL 4.25% peritoneal dialysate plus 1.5mg·kg-1 RGZ daily IP for 5 weeks combined with four injections of erythromycin (62.5mg on days 7, 14, 21, 28); high-dose RGZ group (n=9) received 20 mL 4.25% peritoneal dialysate plus 15mg·kg-1 RGZ daily IP for 5 weeks combined with four injections of erythromycin (62.5mg on days 7, 14, 21, 28). Except for control group, peritoneal catheters were implanted in another forty-five rats. At the end of the study, a 1 hour peritoneal equilibration test was performed and plasma glucose and serum lipids were estimated. Then all the rats were humanely killed. The partial peritoneum tissues of rats were harvested and stained by hematoxylin-eosin and Masson trichrome. The morphology changes of partial peritoneum were examined by light microscopy and the expression of TGFβ1 and CTGF in parietal peritoneum were detected with immunohistochemistry assay. Mesenteric expression of PPARγand FN mRNA was evaluated by RT-PCR.Results1. Nine rats were excluded from further analysis because of clogging of the catheter or peritonitis. There were no differences in plasma glucose, triglyceride, total cholesterol and low density lipoprotein cholesterol among the six groups(P>0.05).2. Compared with control group, the number of peritoneal vessels, peritoneal thickness and the expression of TGFβ1 and CTGF were significantly higher in model group and DMSO group(P<0.05). Administration of RGZ resulted in preserved the number of peritoneal vessels and peritoneal thickness, and reduced the expression of TGFβ1 and CTGF(P<0.05). But there was no significant difference between the low-dose RGZ group and the high-dose RGZ group(P>0.05).3. Compared with control group, PPARγand FN mRNA levels were significantly increased in model group and DMSO group (P<0.05). Up-regulation of the expression of the PPARγand FN mRNA was suppressed by RGZ (P<0.05). No significant difference was observed between the low-dose RGZ group and the high-dose RGZ group (P>0.05).4. Compared with control group, the ultrafilitration volume (UF) and glucose reabsorption (D1/D0) were significantly lower in NS group, model group, DMSO group, low-dose RGZ group, and high-dose RGZ group, and the dialysate-to-plasma urea ratio (D/Purea) were significantly higher (P<0.05). The most significant changes were found in model group and DMSO group.Conclusions1. A type of peritoneal fibrosis model in rats could be successfully established.2. RGZ could ameliorate peritoneal fibrosis and improve the structural and functional parameters of peritoneum.3. RGZ could improve peritoneal fibrosis through PPARγactivation and down-regulation of TGFβ1, CTGF and FN.