Objective: To investigate the effects of cyclooxygenase-2 (COX-2) inhibitor on peritoneal lymphangiogenesis and peritoneum function in uremic rat.
Methods: Uremic rats treated by peritoneal dialysis were intragastric administration celecoxib.Structures of peritoneum, peritoneal function, peritoneal lymphatic vessel density (LVD) were detected in every group. The mRNA of vascular endothelial growth factor-C (VEGF-C), lymphatic vessel endothelial hyaluronan receptor-1(LYVE-1) and COX-2 were tested by RT-PCR. The protein expressions of LYVE-1,VEGF-C, COX-2 were tested by western blot.
Results: With the extension of the duration of dialysis, the peritoneum thickness was increasing, inflammatory cell infiltrated obviously, ultrafiltration volume decreased significantly. But the celecoxib could increase ultrafiltration volume and reduce the glucose transport rate (P < 0.05) . Compared with the normal group, the levels of LVD, COX-2,VEGF-C, and LYVE-1 mRNA and protein were significantly up-regulated in uremic and dialysis groups (P < 0.05). Compared with the uremic dialysis group, the levels of LVD, COX-2,VEGF-C and LYVE-1 mRNA and protein were significantly down-regulated in the celecoxib group. There was a positive correlation between COX-2 and VEGF-C, LVD in protein levels, as well as VEGF-C and LVD(all P values<0.05).
Conclusions: Hyper glucose dialysis solution and uremic condition could up-regulate the expression of COX-2,VEGF-C, LYVE-1 in gene and protein level and stimulate lymphangiogenesis. COX-2 inhibitor could delay the change of peritoneal structures and function. COX-2 inhibitor could prevent the lymphangiogenesis in uremic rat treated by peritoneal dialysis, which might down-regulate the expression of VEGF-C by COX-2 depended manner.