Klotho蛋白通过调控Kear1-Nrf2-ARE信号通路在草酸钙肾结石形成过程中的作用和机制研究

氧化损伤被公认为是草酸钙结石发生发展的一个重要起始环节。但氧化损伤有多种方式和途径。研究表明，Klotho蛋白能够减轻氧化应激对正常细胞的伤害。我们研究发现，Klotho蛋白可以上调Nrf2表达，减轻草酸钙诱导的肾小管上皮细胞氧化损伤和结石晶体形成；提示Klotho蛋白此作用可能和Keap1/Nrf2/ARE通路的激活有关。据此本课题提出“Klotho蛋白在减轻草酸钙晶体对肾小管上皮细胞氧化损伤作用的同时，减少草酸钙晶体对肾小管上皮细胞的粘附成石”这一假说。Klotho蛋白这一作用可能是通过Keap1/Nrf2/ARE信号通路发挥作用的。本研究拟在大鼠肾小管上皮细胞，研究Klotho对草酸钙晶体诱导的肾小管上皮细胞氧化损伤及草酸钙晶体粘附的影响，并与Keap1/Nrf2/ARE信号通路的关系。探讨Klotho在草酸钙结石形成中的作用和机制；为验证该假说提供证据；为防治草酸钙结石提供新依据。

Oxidative damage is recognized as an important starting point for the development of calcium oxalate stone. But there are many ways and means of oxidative damage. Studies have shown that Klotho protein can reduce oxidative stress damage to normal cells. We found that Klotho protein can upregulate the expression of Nrf2, reduce renal tubular epithelial cells oxidative injury and stone crystal formation induced by calcium oxalate; this effect of Klotho protein may be related to the activation of the Keap1/Nrf2/ARE pathway. Based on this hypothesis, this study points that while Klotho protein reduces renal tubular epithelial cells oxidative injury and stone crystal formation induced by calcium oxalate, it can also reduce the adhesion of calcium oxalate crystals to the renal tubular epithelial cells. The role of Klotho protein may be through the Keap1/Nrf2/ARE signaling pathway. This study takes rat renal tubular epithelial cells as the objects, to investigate the effects of Klotho on the oxidative damage of renal tubular epithelial cells induced by calcium oxalate crystals and the adhesion of calcium oxalate crystals and the relationship with Keap1/Nrf2/ARE signaling pathway. To investigate the role and mechanism of Klotho in the formation of calcium oxalate stone, to provide evidence for the hypothesis, and to provide evidence for the prevention and cure of the calcium oxalate stone.