氧化应激在腹膜纤维化大鼠模型腹膜间皮细胞转分化中的作用

目的:研究氧化应激在腹膜纤维化大鼠腹膜间皮细胞转分化中的作用;观察抗氧化剂普罗布考的干预效应.方法:采用4.25%高糖腹透液以100 mL/kg 腹腔注射法复制腹膜纤维化大鼠模型,实验分为正常对照组、生理盐水对照组、腹膜纤维化模型组和普罗布考干预组.4周后行腹膜平衡试验,处死大鼠,准确测量超滤量,检测腹膜功能;取肠系膜...

Epithelial-to-mesenchymal transdifferentiation of peritoneal mesothelial cells mediated by oxidative stress in peritoneal fibrosis rats

Objective To investigate the role of oxidative stress in the epithelial-to-mesenchymal transdifferentiation (EMT) of peritoneal mesothelial cells in rat model of peritoneal fibrosis and the effect of probucol on peritoneal fibrosis. Methods The rat model of peritoneal fibrosis was induced by 4.25% high glucose peritoneal dialysis fluid (PDF). The rats were randomly divided into 4 groups:the control group, the saline group, the peritoneal fibrosis group, and the probucol group. A 4 hour peritoneal equilibration test (PET) was performed 4 weeks later. The peritoneal function and net ultrafiltration (UF) volume were determined. The level of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in peritoneal tissue were examined. The histology of peritoneal membrane was evaluated by light microscopy. E-cadherin and α-smooth muscle actin (α-SMA) protein expression was evaluated by immunohistochemical method and Western blot.Results The mesothelial cells were detached from peritoneal membrane in peritoneal firbosis rats. Comparing with the control rats, the thickness of visceral peritoneum, the level of MDA, and the-SMA protein expression were increased while the net ultrafiltration volume, the level of GSH-Px and E-cadherin protein expression were decreased in peritoneal firbosis rats. All these changes were reversed in the rats treated with probucol.Conclusion Oxidative stress plays an important role in transdifferentiation of peritoneal mesothelial cell in the peritoneal fibrosis rats. Probucol can improve structure and function of peritoneum, and partially reverse the EMT by reducing the oxidative stress.