Effect Of Rosiglitazone On The Expression Of AQP-1、 VEGF-A And COX-2in Uremic Rat Of Peritoneal Dialysis

ObjectiveTo investigate the effect of rosiglitazone(RGZ) on peritoneal morphology, function andthe expression of Aquaporin1(AQP-1),vascular endothelial growth factor A(VEGF-A) andcyclooxygenase2(COX-2) in uremic rat of peritoneal dialysis.MethodsThirty Sprague-Dawley rats were randomly divided into five groups. Group S (n=6) wassubjected to sham operation. Group N (n=6) was subjected to nephrectomy with siliconcatheter inserted，but no peritoneal exposure. Group P (n=6) was subjected to nephrectomywith silicon catheter inserted and receiving daily peritoneal injection through the catheter,using4.25%peritoneal dialysis fluid10ml twice a day for2weeks. Group R (n=6) wassubjected to nephrectomy with silicon catheter inserted and receiving daily peritonealinjection through the catheter, using4.25%peritoneal dialysis fluid containingrosiglitazone(0.2mg/kg)10ml twice a day for2weeks. Group GW (n=6) was subjected tonephrectomy with silicon catheter inserted and receiving daily peritoneal injection through thecatheter, using4.25%peritoneal dialysis fluid containing rosiglitazone(0.2mg/kg) andGW9662(0.2mg/kg)10ml twice a day for2weeks. After two weeks of dialysis,a90minperitoneal equilibration test was performed and the amount of ultrafiltration were accuratelymeasured. Value of sodium(D-Na) and creatinine(D-cr) in peritoneal effluent, plasma sodium(P-Na), plasma creatinine (P-cr), the initial dialysis liquid glucose (D0) and the glucose (D1)in peritoneal effluent were measured, and the D/P-Na, D/P-cr, D1/D0were calculated.Thepartial peritoneum tissues of rats were harvested and stained by hematoxylin-eosin(HE),thenmorphology changes of partial peritoneum were examined by light microscopy. Theexpression of AQP-1,VEGF-A and COX-2in omentum were detected withimmunohistochemistry assay．AQP-1, VEGF-A and COX-2mRNA changes were detectedby qRT-PCR. Results1.Two rats were excluded at the end of the study, however, there was no episode ofinfection in any group.2.Morphology changes of partial peritoneum showed that compared with Group S，adramatic increase in thickness of the mesothelium-to-muscle layer of peritoneum in GroupN,P,R and GW(P<0.05);compared with Group P,the thickness significantly decreased inGroup R(P<0.05).3.PET results showed that,compared with Group S, ultrafiltration (UF) and D1/D0significantly reduced,while D/P-cr and D/P-Na increased significantly in Group P, R, andGW(P<0.05);compared with Group P, ultrafiltration and D1/D0significantly increased,while D/P-cr significantly reduced in Group R(P<0.05).4.Expression of AQP1, VEGF-A, COX-2were detected in each group.Compared withgroup S, expression of AQP1, VEGF-A and COX-2mRNA and protein were significantlyincreased in Group P, R and GW(P<0.05);Compared with group P,expression of AQP1,VEGF-A mRNA and protein were significantly decreased in Group R andGW(P<0.05);Compared with group P,expression of COX-2mRNA and protein weresignificantly decreased in Group R(P<0.05),while no differences in the expression of COX-2mRNA and protein in Group GW (P<0.05).Expression of AQP1, VEGF-A mRNA andprotein in each group were positively correlated (P<0.05).Conclusions1.Our study successfully reproduced a uremic rat model of peritoneal dialysis;2.Rosiglitazone can inhibit peritoneal interstitial and vascular proliferation, protectperitoneal function and increase ultrafiltration;3.Rosiglitazone can inhibit the expression of AQP-1, expression of AQP1and VEGF-Acorrelated positively;4.Rosiglitazone can protect peritoneal function probably by inhibiting expression ofVEGF-A and COX-2.