Effects of cyclooxygenase-2 inhibitor on peritoneal function and angiogenesis in uremic peritoneal dialysis rats / 中华肾脏病杂志

ABSTRACT

Objective To investigate the effects of the cyclooxygenase-2 (COX-2) inhibitor (celecoxib) on angiogenesis and peritoneal function of uremic peritoneal dialysis rats.Methods Forty-eight male SD rats were selected,and they were randomly divided into five groupsnormal control group(n =8),sham operation group(n =8),uremia group(5/6 nephrectomy,n =8),PD group [4.25％ PD solution,2 weeks PD model(n =8) and 4 weeks PD model(n =8)],PD + celecoxib intervention group[treated by celecoxib(20 mg/kg) via oral gavage,n =8].The peritoneum of uremic peritoneal dialysis rats was observed in different dialysis time from peritoneal structures,functions,peritoneal tissue capillary density (microvessel density,MVD) and COX-2,vascular endothelial growth factor (VEGF) expression level,and the impacts of celecoxib on uremic peritoneal dialysis rats peritoneal angiogenesis and peritoneal function were study.Results With the conduct of the peritoneal dialysis,peritoneal thickness increased,the inflammatory cells infiltrated,peritoneal equilibration test (PET) showed that ultrafiltration volume decreased significantly (P ＜ 0.05),the amount of glucose transport rate rised significantly (P ＜ 0.05),but the celecoxib could improve net ultrafiltration volume (P ＜ 0.05),and reduce the glucose transport rate (P ＜ 0.05).The peritoneal tissue MVD and COX-2,VEGF expression were significantly increased in uremia group and PD group compared with that in the normal control group (all P ＜ 0.05),were significantly lower in PD + Celecoxib intervention group than that in uremia group (P ＜ 0.05).The correlation analysis showed that the level of COX-2 protein expression with MVD,VEGF protein expression was positively correlated (both P ＜ 0.05),the level of VEGF protein expression and MVD was positively correlated (P ＜ 0.05).Conclusions In vivo high glucose dialysate and uremia environmental can stimulate the COX-2 and VEGF expression raised,and the capillaries production increased in peritoneal tissue.Celecoxib can alleviate the change of peritoneal tissue morphology and function in long-term peritoneal dialysis rats.Celecoxib inhibits the peritoneal neovascularization of uremic peritoneal dialysis rats,possibly through inhibition of COX-2 expression to reduce the production of VEGF.