Effect of rosiglitazone on the expression of AQP-1, VEGF-A and COX-2 in uremic rat of peritoneal dialysis

Abstract

Objective To investigate the effect of rosiglitazone(RGZ) on peritoneal morphology, function and the expressions of Aquaporin 1 (AQP-1), vascular endothelial growth factor A(VEGF-A) and cyclooxygenase 2(COX-2) in uremic rat of peritoneal dialysis. Methods Thirty Sprague-Dawley rats were randomly divided into five groups. Group S (n=6) was subjected to sham operation. Group N (n=6) was subjected to nephrectomy with silicon catheter inserted, but no peritoneal exposure. Group P (n=6) was subjected to nephrectomy with silicon catheter inserted and receiving daily peritoneal injection through the catheter, using 4.25% peritoneal dialysis fluid 10 ml twice a day for 2 weeks. Group R (n=6) was subjected to nephrectomy with silicon catheter inserted and receiving daily peritoneal injection through the catheter, using 4.25% peritoneal dialysis fluid containing rosiglitazone (0.2 mg/kg) 10 ml twice a day for 2 weeks. Group GW (n=6) was subjected to nephrectomy with silicon catheter inserted and receiving daily peritoneal injection through the catheter, using 4.25% peritoneal dialysis fluid containing rosiglitazone (0.2 mg/kg) and GW9662 (0.2 mg/kg) 10 ml twice a day for 2 weeks. After two weeks of dialysis, a 90 min peritoneal equilibration test was performed and the amount of ultrafiltration was accurately measured. The partial peritoneum tissues of rats were harvested and stained by hematoxylin-eosin (HE), then morphology changes of partial peritoneum were examined by light microscopy. The expression of AQP-1,VEGF-A and COX-2 in omentum were detected with immunohistochemistry assay. AQP-1, VEGF-A and COX-2 mRNA were detected by qRT-PCR. Results Morphology changes of partial peritoneum showed that compared with Group S, a dramatic increase in thickness of the mesothelium-to-muscle layer of peritoneum in Group N, P, R and GW(P<0.05). Compared with group P, the thickness significantly decreased in Group R(P<0.05). PET results showed that compared with Group S, ultrafiltration (UF) significantly reduced in Group P, R, and GW(P<0.05). Compared with Group P, ultrafiltration significantly increased in Group P, R, and GW (P<0.05). Compared with group S, the expressions of AQP1, VEGF-A and COX-2 mRNA and protein were significantly increased in group P, R and GW(P<0.05). Compared with group P, the expressions of AQP1, VEGF-A mRNA and protein were significantly decreased in Group R and GW(P<0.05). Compared with group P, the expressions of COX-2 mRNA and protein were significantly decreased in group R (P<0.05), while no differences in the expression of COX-2 mRNA and protein in group GW (P<0.05). Conclusions Rosiglitazone can inhibit peritoneal interstitial and vascular proliferation, protect peritoneal function and increase ultrafiltration. Rosiglitazone can protect peritoneal function probably by inhibiting expression of VEGF-A and COX-2. Key words: Peritoneal dialysis; VEGF-A; COX-2; AQP-1; Rosiglitazone