Prevention of glomerulosclerosis through the regulation of isoprostane pathway

肾小球硬化已被广泛认识到在终末期肾衰竭患者的肾脏需要肾脏替代治疗。最近，人们推测氧化应激可能在肾小球硬化的发病机制中起作用。在这项研究中，我们使用氧化应激产生的异前列腺素研究了氧化应激在肾小球硬化症进展中的作用。（1）干扰素γ可通过激活S1AT途径，增强NADPH氧化酶的活性，从而增加体外培养的人肾小球系膜细胞超氧阴离子的产生。(2)In具有超氧化物歧化酶活性的Tempol和血管紧张素AT 1受体阻断剂可显著抑制Dahl盐敏感大鼠血压升高和尿蛋白排泄，并改善肾小球进行性改变。（3）磷酸二酯酶10AmRNA在大鼠肾小球上皮细胞中有特异性分布。（4）慢性血液透析患者因透析本身而暴露于更多的氧化应激，使用生物相容性维生素E涂层透析膜或服用维生素E可降低这种氧化应激，这些结果表明氧化应激在肾小球硬化的进展中起重要作用。未来的研究需要评估磷酸二酯酶活性和氧化应激在肾小球硬化发病机制中的关系。

Glomerulosclerosis has been widely recognized in the kidney of end-stage renal failure patients requiring renal replacement therapy. Recently, it has been postulated that oxidative stress may play a role in the pathogenesis of glomerulosclerosis. In this study, we examined the role of oxidative stress in the progression of giomerulosclerosis using oxidative stress-generated isoprostane.(1)Interferon y significantly increased the production of superoxide anion in cultured human mesangial cells by enhancing the NADPH oxidase activity via the activation of S1AT pathway.(2)In Dahl salt-sensitive rats, tempol, which possess the activity similar to superoxide dismutase, and angiotensin AT1 receptor blockade significantly inhibited the increase of blood pressure and urinary protein excretion, and ameliorated progressive sclerotic glomerular changes.(3)Specific distribution of phosphodiesterase 10A mRNA, which catalyzes the hydrolysis of cyclic nucleotide second messengers, was observed in glomerular epithelial cells in rat kidney.(4)Chronic hemodialysis patients are exposed to more oxidative stress through dialysis itself and this oxidative stress decreased by the use of biocompatible vitamin E coated dialysis membrane or vitamin E administration.These results demonstrate that oxidative stress plays an important role in the progression of glomerulosclerosis. Future studies are required for evaluating the relation between phosphodiesterase activity and oxidative stress in the pathogenesis of glomerulosclerosis.