高醣腹膜透析液及發炎細胞激素對腹膜間皮細胞前列腺素、血管內皮細胞生長因子的作用:COX抑制劑的影響

Abstract

八､論文英文簡述（Summary） Background. The structural and functional changes in peritoneum always bothered the patients reveiving long-term continuous ambulatory peritoneal dialysis (CAPD). It was suggested that human peritoneal mesothelial cells (HPMCs) contribute to the production of vascular endothelial growth factor (VEGF),which may enhance vasodilation, vascular permeability, and neoangiogenesis in peritoneal membrane. The present study was designed to evaluate the influence of high glucose dialysis solution and porinflammatory cytokine on prostaglandin and VEGF production in HPMC and the influence of cyclooxygenase (COX) inhibitor. Methods. HPMCs were cultured from human omentum by an enzyme digestion method. High glucose dialysis solution (Dianeal 1.5%, 2.5%, 4.25%) , IL-1β(1, 5 ng/ml) , PGE2 ,and High glucose dialysis solution /IL-1β with COX inhibitor were tested in cultured HPMCs respectively. Expression of COX-2 and PGE2 proteins were dteremined by Western blot and EIISA. VEGF-A was measured in cell supernatant by ELISA and VEGF-C were measured by Western blot and VEGF-A,C,D mRNA expressions were evaluated by RT-PCR. Results. High glucose dialysis solution (Dianeal 1.5%, 2.5%, 4.25%) and IL-1β( 1, 5 ng/ml) enhanced the VEGF-A, COX-2, PGE2 expression in HPMC culture; but were not able to up-regulate the VEGF-C or D. High glucose dialysis solution (Dianeal 1.5%, 2.5%, 4.25%) and IL-1β(1, 5 ng/ml) in HPMC culture with COX inhibitor was not able to down-regulate the VEGF-A even with the reduction of PGE2 level. PGE2 was not able to up-regulate the VEGF-A in HPMC culture. COX inhibitor failed to inhibit the VEGF-A produced by the high glucose dialysis solution and IL-1β in HPMC culture. We studied the PGE2 receptors distributed on the surface of HPMC. EP3 and EP4 receptors predominate on HPMC surface. In the present study, the VEGF-C production increased while peritoneal fibroblasts cultured with high glucose dialysis solution and the increment of VEGF-C could be inhibit by COX inhibitor (NS398). Conclusion. The VEGF up-regulated by the high glucose dialysis solution and IL-1β in HPMC culture is VEGF-A, not VEGF-C or VEGF-D. VEGF-C production increased while peritoneal fibroblasts cultured with high glucose dialysis solution and the increment of VEGF-C could be inhibited by COX inhibitor (NS398). COX inhibitor failed to inhibit the VEGF-A expression by HPMCs cultured with high glucose dialysis solution and IL-1β. PGE2 was not able to up-regulate the VEGF-A production in HPMC culture. In the future studies, we will try to elucidate the relationship between the VEGF-C produced by peritoneal fibroblasts and the peritoneal ultrafiltration failure or peritoneal lymphatic absorption .