The Abnormal Expression Of Tristetraprolin And VEGF Family Lead To UFF

Background and ObjectivePeritoneal dialysis (PD) is an effective renal replacement therapy for patients with end-stage renal disease (ESRD). However, with prolonging exposure to non-biocompatible dialysis fluids, the peritoneal ultrafiltration ability of PD patients will gradually decline, and finally the ultrafiltration failure (UFF) occured. Vascular endothelial growth factor (VEGF) can promote angiogenesis, which lead to an increase of peritoneum material transport area coefficient (MTAC),and then lead to the UFF. This mechanism is a research focus in recent years. Lymph reabsorption increase as well is one of the mechanisms the occurrence of UFF, however, the research of the lymphangiogenesis lags behind angiogenesis. Ever so,there are few researches on members of VEGF family--VEGF-C/VEGF-D,which promote lymphangiogenesis, increase lynph reabsorption. Tristetraprolin (TTP) as an inflammatory regulatory factor, can regulate the expression of VEGF in gastrointestinal cancer and breast swelling, but TTP whether be involved in the regulation of the abnormal expression of the VEGF family or not in PD peritoneum, which has not been seen any studies.Therefore,we established the peritoneal dialysis uremic rats model on basis of5/6nephrectomy to imitate the environment of uremic and intraperitoneal long-term PD procedure, to observe the expression of TTP and VEGF family,and to test and verify lymphangiogenesis was involved in the occurrence of UFF as well as angiogenesis.Methods1.Forty male SD rats of clean grade were selected (180-200g), The uremic rats model was established by5/6nephrectomy, and of which the PD rats modle was established on the basis.2.These SD rats were divided into five groups randomly:Anormal group, sham operation group, uremia group, PD2-week group and PD4-week group. The rats of PD2-week group and PD4-week group were given regular peritoneal dialysis with4.25%peritoneal dialysis fluid in dose of3ml/100g BW.PD2-week group for2weeks, PD4-week group for4weeks.3. Before the rats were euthanized, they was given peritoneal equilibration test (PET), calculate the the mass transfer of glucose and peritoneal ultrafiltration volume.4.1mmunohistochemical staining was applied to detect the protein expressions of VEGF, VEGF-C in each groups of rats’parietal peritoneum,microvessel density (MVD) and lymphatic vessel density(LVD) of peritoneal tissue was used and quantified with anti-CD31antibody,anti-LYVE-1. antibody.5.Reversetranscription polymerase chain reaction(RT-PCR) methods were applied to detect the mRNA expressions of VEGF-A VEGF-B、VEGF-C. VEGF-D、 TTP; western blotting was used to detect the protein expression of TTP.Results1. PET revealed that, compared with normal group, the mass transport of glucose of both PD2-week group and PD4-week group elevated(P<0.05), and compared with PD2-week group, PD4-week group’s elevated(F<0.05). However,the peritoneal ultrafiltration volume of both PD2-week group and PD4-week group reduced comparing to normal group, and compared with PD2-week group, PD4-week group ’s reduced(P<0.05).2. Compared with normal group, the protein expression of CD31,LYVE-1were increased in and PD4-week groups(P<0.05).Those of PD4-week groups likewise were increased compared to uremia group(P<0.05). Compared with normal group, the count of MVD and LVD were increased in in uremia group and PD4-week groups(P<0.05), and those of PD4-week group were also increased compared to uremia group(P<0.05).3. Compared with normal group, the mRNA expressions of VEGF, VEGF-A,VEGF-B, VEGF-C,VEGF-D were significantly increased in uremia group and PD4-week group (P<0.05), compared with uremia group, the expressions of PD4-week group were significantly increased(P<0.05).4. Compared with normal group, the mRNA expressions of VEGF,VEGF-C were increased in both PD2-week group and PD4-week group(P<0.05), compared with uremia group, the expressions of PD group were increased(P<0.05).. Compared with normal group, the protein expressions of VEGF,VEGF-C were increased in both PD2-week group and PD4-week group(P<0.05), compared with uremia group, the expressions of PD group were increased(P<0.05).5. Compared with normal group, the expressions TTP was decreased in uremia group and PD group (P<0.05); compared with uremia group, the expressions of PD group was significantly decreased (P<0.05). Compared with normal group, the expressions of TTP was decreased in PD2-week group and PD4-week group(P<0.05); compared with PD2-week group, the expressions of PD4-week group was significantly decreased (P<0.05)Conclusions1. High glucose peritoneal dialysis fluid and uremic circumstance result in the expression of TTP and VEGF family changes in a PD time-dependent manner.2. High glucose peritoneal dialysis liquid gave rise to angiogenesis and lymphangiogenesis, both of which led to UFF.