Effect Of Oxidative Stress On The Transdifferentiation Of Peritoneal Mesothelial Cell In Rat Model Of Peritoneal Fibrosis And The Intervention Study Of Probucol

BackgroundUltrafiltration failure due to peritoneal fibrosis is one of the most important reasons for discontinuation of peritoneal dialysis. Epithlial-mesenchymal transition(EMT) is the basis of peritoneal fibrosis. High glucose may induce oxidative stress in human peritoneal mesothelial cells and promote peritoneal fibrosis.Probucol has the effect of anti-inflammatory,antioxidantion and protective effect of kidney.ObjectivesThe present study investigates the role of oxidative stress in EMT of peritoneal fibrosis rats and the protective effect of probucol to clarify the cause of peritoneal fibrosis and ultrafiltration failure.MethodsTwenty-four Sprague-Dawley(SD) rats,were divided into four groups:group 1(control,n=6);group 2(normal saline,n=6);group 3 (4.25%dextrose solution,n=6);group 4(4.25%dextrose solution+1% probucol in diet,n=6).Over a period of 28 days,the animals in different group received a daily infusion of different dialysate.A 4-hour peritoneal equilibration test(PET) was performed with 25 ml 4.25%dextrose dialysate.Dialysate-to-plasma creatinine ratio(D/P),glucose reabsorption (D₄/D₀),net ultrafiltration(UF),mass transfer glucose(MTG),the level of malondialdehyde(MDA) and glutathione peroxidase(GSH-Px). Peritoneal membrane histology was evaluated by light microscopy.EMT was evaluated by immunohistochemical methods of E-cadherin andα-SMA.ResultsThe D₄/D₀ ratio and net ultrafiltration volume in group 3 was significantly lower than groups 1,2 and 4(P＜0.05).The D/Pcr ratio and MTG in group 3 was significantly higher than groups 1,2 and 4(P＜0.05). The thickness of the peritoneal membrane in group 3 was significantly greater than in groups 1,2 and 4(P＜0.001).The level of MDA in group 3 was significantly higher and the level of GSH-Px in group 3 was lower than groups 1,2 and 4(P＜0.01).There is continuousα-SMA expression and no E-cadherin expression in group 3.There is discontinuousα-SMA expression and E-cadherin expression in group 4.ConclusionOxidative stress may play a role in the EMT of rat.Probucol can improve the transport function of rat peritoneum,reverse EMT of rat partially,have the protective effect of peritoneum in rat model of peritoneal fibrosis.