| BACKGROUNDIn the recent 20 years, Peritoneal dialysis (PD) is an established renal replacement therapy in end stage renal disease. High technique failure rate is the main restrictions for the development of peritoneal dialysis. So how to improve the technique survival rate has drawn great interests. Long-term peritoneal dialysis is associated with the development of functional and structural alterations of the peritoneal membrane which may lead to inadequate dialysis.Fibrosis and neoangiogenesis are the most important physiological changes of peritoneum, and also the main factors influencing peritoneal function. Many growth factors and cytokines play important role in it. Hyper expression of transforming growth factor-beta (TGF-beta) is of intense relation to fibrosis of peritoneum; vascular endothelial growth factor is essential for hyperpermeability and eoangiogenesis alterations of the peritoneal membrane; Matrix Metalloproteinase (MMP) and it tissue inhibitor (TIMP) take place in degradation and remodeling of the connective tissue andinflammatory reactions.Renin-angiotensin systems(RAS) wildly exists in the body and exert variety of functions. The interaction of angiotensin II with its ligand can be blocked by angiotensin II receptor antagonist. Losartan is a selective non-peptide angiotensin II receptor binding inhibitors and selectively inhibits all Ang II responses that have been studied. Compared with peptide Ang II antagonists (e.g. saralasin), losartan has significant advantages, including a long duration of action, effective oral absorption and no Ang II agonist activity.RAS antagonist has now been introduced into the PD, but its influence on the peritoneal membrane (PM) remains debated. Go. M et. al demonstrated that Angll can influence the peritoneal ultrafiltration and lymph reabsorbtion in the rat model. Sawada reported RAS antagonist could protect peritoneum from sclerosis. Imai found ACEI or ARB had inverse effect on peritoneal ultrafiltration function. Until now .there neither has any large sample control research nor molecular biologic explanation on it. The aim of the present study was to determine the functional and structural alterations of the peritoneal membrane in long-term PD model of rat , and to assess the effect of angiotensin II receptor antagonist-losartan on peritoneum in long-term PD. In addition, we followed the expression of growth factors in the peritoneum of SD rats. MATERIALS AND METHODSExperiments were performed on adult male Sprague-Dawley rats weighing 180~240g. Rats were randomized into 5 groups randomly and dialyzed with various solution as follows: (l)no solution(control group, n=8), (2)0.9% Saline solution (NS group ,n=8), (3)4. 25% Dianeal solution(PD group, n=13) ,(4) 4.25% Dianeal solution, plus oral administration of losartan 20 mg/kg(0group, n-13), (5) 4.25% Dianeal solution, plus intraperitoneal injection losartan 20 mg/kg (I group, n=13)Peritoneal equilibration tests, ultrafiltration function and mass transfer area coefficients (MTAC) of creatinine were performed 8 weeks later .In the histological examination, the peritoneal membrane section were fixed in 10% buffered formalin solution. Paraffin sections were cut and stained by hematoxylin & eosin and Masson trichrome. Peritoneal interstitial thickness was measured from the inner surface of the muscle to the mesothelium, inflammation, fibroblastic activity and neovascularization were defined by counting mononuclear cells, fibroblasts, and capillaries per high-power field at 400 X magnificat ion.Dialysate TGF 1 and VEGF levels were measured using a commercial available enzyme-linked immunosorbent assay kit. Dialysate CA125 level was determined using a microparticle enzyme immunoassay.RT-PCR was used to analyze the expression of mRNA coding for TGF-3, VEGF,MMP-2 and TIMP-2 in peritoneum. RESULTSAdministration of 4. 25% Dianeal PD solution into the peritoneal cavity for 8 weeks alters peritoneal structure and affects function, such as decrease D/D0 glucose ratio(P<0.05), incr...
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