Effect Of Losartan On The Expression Of TLR4 In Peritoneal Fibrosis Of Rat Peritoneal Dialysis Model

1 Establishing a peritoneal fibrosis rat modelObjective To establish models of peritoneal fibrosis and observe their general condition, Levels of TLR4, IL-6, IL-8 expression and pathological changes of peritoneum induced by intraperitoneal injections of 4.25% Dianeal in rats.Methods 30 male SD rats were randomly divided into three groups:2 weeks model,4 weeks model and 6 weeks model, Rats were treated with daily intraperitoneal injections of 4.25% Dianeal (100ml/kg) over a period of 42 days, the other 10 normal rats were raised as normal control group. Animals were sacrificed after 14 days,28 days and 42 days. Peritoneal equilibrium test (PET) of 4-hour dwell was performed. The parietal and visceral peritoneum samples were harvested for regular histological evaluation after PET. The expression of TLR4, IL-6, and IL-8 in peritoneal tissue was detected by immunofluorescence.Results Normal peritoneum was covered with a layer flat mesothelial cell. Comparing with the rats in normal group, the peritoneum thickness and collagen deposition was significantly increased in the 2 and 4 weeks model (P<0.01), the ultrafiltration was descend and mass transport of glucose was increased significantly (P<0.01). and the expression of TLR4, IL-6, IL-8 was upregulated in model group. A significant impairment in ultrafiltration with associated increase of mass transport of glucose out of the peritoneum was also noted. But there was no significant difference between 4 and 6 weeks model.Conclusion The activation of TLR4, IL-6, IL-8 protein induced by 4.25% Dianeal was involved in peritoneal fibrogenesis process, the fibrosis model presents a persistent and slow progress in 6 weeks model, the model is succeed when it is 4 weeks. Thus it gives us a basic model to investigate therapy for peritoneal fibrosis.2 Effect of Losartan on the Expression of TLR4 in Peritoneal Fibrosis of Rat peritoneal Dialysis ModelObjectives Establish a model of Peritoneal Fibrosis in Rat related to peritoneal Dialysis to investigate the effects of Losartan tablet on expression of TLR4, IL-6, IL-8 on peritoneum in the Model. Materials and Methods Thirty male SD rats were randomly divided into the following three groups:control group (n=10), model group (n=10) and losartan-treated group (n=10). Rats were treated with daily intraperitoneal injections of 4.25% Dianeal (100ml/kg) over a period of 28 days. rats were fed with Losartan tablet (30mg/kg/d) besides injections of Dianeal in losartan-treated group, rats in control group were fed normolly, All rats were sacrificed at the end of 4 weeks. Peritoneal equilibrium test (PET) was performed. the ultrafiltration was detted, and mass transport of glucose was also calculated, The parietal and visceral peritoneum samples were harvested for regular histological evaluation after PET. The expression of TLR4, IL-6, IL-8 in peritoneal tissue was detected by immunofluorescence.Results Compared with the model and normal group, after treated with losartan, the thickness of parietal perineum was shorted clearly(p<0.01), the ultrafiltration was improved, and mass transport of glucose was also decreased(p<0.01). A significant downregulated of TLR4, IL-6, IL-8 was also observed in the treated rats.Conclusion Losartan can down-regulated the expression of TLR4, IL-6, IL-8 during peritoneum in the treated group, reverse the peritoneal sclerosis partly, and improve function of ultrafiltration and glucose transfer.