Effect of rosiglitazone on the expression of AQP-1, VEGF-A and COX-2 in uremic rat of peritoneal dialysis / 中华肾脏病杂志

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.