| Backgroud and ObjectiveEnd-stage renal disease (ESRD) has become one of the major public health problems which human must face in the 21st century. Peritoneal dialysis (PD) is one of the effective ways for end-stage renal disease patients, who need accept renal replacement therapy to survive. Because peritoneal dialysis has its own advantages, such as a simple and convenient operation, a lower hepatitis C infection rate, a small hemodynamic effect, better residual renal function protecting effect, etc., it has become the preferred alternative treatment for many ESRD patients. However, there was appeared peritoneal angiogenesis and increased permeability for a long-term PD patients which may be involved in ultrafiltration failure(UFF).Ultrafiltration failure has become one of the most important reasons that PD patients drop out. Peritoneal angiogenesis was found on the peritoneum of PD patients who lost their ultrafiltration capacity. Peritoneal angiogenesis plays a key role in the occurrence of ultrafiltration failure.Angiopoietin-2/Tie-2 was recently identified endothelial cell-specific, ligand-receptor system which plays an important role in the initiation of pathological neoangiogenesis.Souble Tie2 fusion protein (sTie-2/Fc) was the ectodomains of Tie-2 as recombinant fusion proteins which could competitively inhibited the binding of angiopoietin-2 to Tie-2. Therefore,we established the peritoneal dialysis uremic rats model to imitate the peritoneal dialysis procedure of human.The treatment group rats were given recombinant rat soluble Tie2 fusion protein. By observing the expressions of Angpt-2 and microvessel density in rats'peritoneum, we wanted to see the effect of recombinant rat soluble Tie2 fusion protein and tried to explore the potential mechanism of soluble Tie2 fusion protein inhibiting peritoneal angiogenesis. The aim was to prevent and treat peritoneal ultrafiltration failure, provide experimental basis for clinical treatment.Methods48 male SD Rats were randomly divided into 6 groups:normal rats as control group (group1), rats with sham operation (group2), uremic rats without PD (group3), uremic rats dialyzed with 4.25% PD solution (group4), uremic rats dialyzed with 4.25% PD solution and treated by subcutaneous injection of 0.25ug/100g soluble Tie2 fusion protein (group5), uremic rats dialyzed with 4.25% PD solution and treated by subcutaneous injection of 0.50ug/100g soluble Tie2 fusion protein (group6). Soluble Tie2 fusion protein was given every other day during peritoneal dialysis period, total 14 doses. After regular PD for 28 days, tissue immunohistochemical staining and RT-PCR were used to detect the protein and mRNA expressions of Angpt-2 in peritoneal tissues in each groups of rats. Microvessel density (MVD) of peritoneal tissue was detected and quantified with immunohistochemical staining by using anti-CD34 antibody.Results1.The expression of Angpt-2 both in protein and mRNA level was found in each group. There was no significant'difference of Angpt-2 expression both in protein and mRNA level between groupl and group2.Compared with group1, the protein and mRNA expression of Angpt-2 were significantly increased in group3 and group4 (all P<0.05). Compared with group3, the protein and mRNA expression of Angpt-2 were significantly increased in group4 (P<0.05). Compared with group 4, the protein and mRNA expression of Angpt-2 were significantly decrease in group5 and group6 (all P<0.05). Compared with group5, the protein and mRNA expression of Angpt-2 were significantly decreased in group6 (P<0.05)2.Only few new microvessel was found in group 1 and group2. Compared with group 1, MVD was significantly up-regulated in group3 and group4 (all P<0.05) Compared with group4, MVD was significantly down-regulated in group5 and group6 (all P<0.05)3.There was a positive correlation between Angpt-2 and MVD in protein level.Conclusions1. The expression of Angpt-2 both in protein and mRNA level might be up-regulated by high glucose and bioincompatible peritoneal dialysis liquid and uremic circumstance. The up-regulating of Angpt-2 in uremic peritoneal dialysis rats peritoneum might involve with the increasement of the peritoneum neoangiogensis and then cause the appearance of ultrafiltration.2. Peritoneum neoangiogensis can be effectively inhibited by soluble Tie2 fusion protein in uremic rat treated with PD. |
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