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The elucidation of crystal formation mechanism through the renal tubular epithelial cell injury and mitochondria injury

通过肾小管上皮细胞损伤和线粒体损伤阐明晶体形成机制

基本信息

批准号：
23791770
负责人：
HIROSE Masahito
金额：
$ 2.66万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2011
资助国家：
日本
起止时间：
2011 至 2012
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791770/
关键词：
尿路結石女性ホルモン酸化ストレス細胞障害ミトコンドリア

项目摘要

In this study, to elucidate about crystal formation mechanism and the low stone prevalence of the woman, I examined sex differences of crystal formation from oxidative stress and cell injury. Besides, it was aimed for development of new stone prevention by elucidating a relation with a cell injury and the oxidation stress. In the study in 2011, I studied sex differences judging from a renal tubule cell and a mitochondrial injury. I gave an oxalic acid precursor to male and female mice, and clarified a difference of the sex about a renal tubule cell and a mitochondrial injury. In stone model mouse, after oxalic acid precursor administration, mitochondria and microvilli of the renal tubular cell collapsed, aggregated in the renal tubular lumen, and crystal nuclei appeared. With the female mouse, these form changes passed slightly late in comparison with a male. In 2012, I examined osteopontin (OPN) which was a stone-related gene. The expression of OPN in the female mouse had less expression than a male before the crystal formation, and expression increasing was slow. Furthermore, a renal tubular microstructure change was slower than wild type after the treatment of the oxalic acid precursor in the examination using knockout mouse, and there were few cell disorders. And there was little quantity of crystal formation. In the female OPN knockout mouse, there was little quantity of crystals more than male. The results of the study clarified the stone formation mechanism and the importance of mitochondrial injury and oxidative stress. Possibility of the new stone prevention through the mitochondria protection was thought. And these were thought one of the new function of the female hormone.

在本研究中，为了阐明晶体形成机制和女性低结石患病率，我研究了氧化应激和细胞损伤下晶体形成的性别差异。此外，通过阐明细胞损伤与氧化应激的关系，旨在开发新的结石预防方法。在2011年的研究中，我通过肾小管细胞和线粒体损伤来研究性别差异。我给雄性和雌性老鼠注射草酸前体，澄清了肾小管细胞和线粒体损伤的性别差异。在石模型小鼠中，草酸前体给药后，肾小管细胞线粒体和微绒毛塌陷，在肾小管腔内聚集，出现晶核。与雄性老鼠相比，雌性老鼠的这些形态变化发生得稍晚。2012年，我检查了骨桥蛋白（OPN），这是一种与结石相关的基因。OPN在雌性小鼠晶体形成前的表达量低于雄性小鼠，且表达量增加缓慢。在敲除小鼠检查中，草酸前体处理后的肾小管微观结构变化比野生型慢，细胞紊乱少。而且几乎没有形成晶体。在雌性OPN基因敲除小鼠中，结晶体数量比雄性少。本研究结果阐明了结石的形成机制以及线粒体损伤和氧化应激的重要性。研究人员认为，新的结石预防可能是通过线粒体的保护。这些被认为是女性荷尔蒙的新功能之一。