Renal tubular epithelial cell injury and oxidative stress induce calcium oxalate crystal formation in mouse kidney
Renal tubular epithelial cell injury and oxidative stress induce calcium oxalate crystal formation in mouse kidney
复制标题
DOI：
10.1111/j.1442-2042.2009.02410.x
复制
发表时间：
2010-01-01
影响因子：
2.6
通讯作者：
Kohri, Kenjiro
中科院分区：
文献类型：
--
作者：
Hirose, Masahito;Yasui, Takahiro;Kohri, Kenjiro
目的：阐明肾小管细胞（RTC）损伤和氧化应激在小鼠模型肾草酸钙晶体形成早期的作用。方法：对8周龄小鼠每日腹腔注射乙醛酸盐（1.35 mmol/kg/天），持续6天。在注射乙醛酸盐之前和之后6、12和24小时以及3和6天提取肾脏。使用皮佐拉托染色和偏光光学显微镜检测晶体形成。对超氧化物歧化酶、4-羟基壬烯醛和丙二醛进行免疫组织化学染色和蛋白质印迹，以分别观察氧化应激和脂质过氧化。使用透射电子显微镜观察 RTC 微观结构损伤和晶核形成。为了改善 RTC 损伤，在乙醛酸给药前 1 周和给药后 1 周用绿茶治疗小鼠。观察晶体数量和RTC损伤情况，并比较乙醛酸给药和未给药绿茶的小鼠。结果：6小时后观察到氧化应激和脂质过氧化。 24小时后，肾远端肾小管腔内出现含有塌陷线粒体和塌陷微绒毛的晶核。第3天检测到占据管腔的晶体。接受绿茶的小鼠中晶体的数量显着低于仅接受乙醛酸盐的小鼠。结论：RTC损伤，特别是线粒体损伤和氧化应激诱导小鼠草酸钙晶体形成的早期阶段。
Objectives:To clarify the role of renal tubular cell (RTC) injury and oxidative stress in the early stage of renal calcium oxalate crystal formation in a mouse model.Methods:Daily intra-abdominal injections of glyoxylate (1.35 mmol/kg/day) into 8-week-old mice were carried out over 6 days. Kidneys were extracted before and at 6, 12 and 24 h and 3 and 6 days after glyoxylate injection. Crystal formation was detected using Pizzolato staining and polarized light optical microscopy. Immunohistochemical staining and western blotting of superoxide dismutase, and 4-hydroxynonenal and malondialdehyde were carried out in order to observe oxidative stress and lipid peroxidation, respectively. RTC microstructural damage and crystal nuclei formation were observed using transmission electron microscopy. To ameliorate RTC injury, mice were treated with green tea 1 week before and 1 week after glyoxylate administration. The number of crystals and RTC damage were observed and comparisons were made between glyoxylate-treated mice with and without green tea administration.Results:Oxidative stress and lipid peroxidation were observed after 6 h. Crystal nuclei containing collapsed mitochondria and fallen microvilli appeared in the renal distal tubular lumen after 24 h. Crystals occupying the tubular lumen were detected on day 3. The number of crystals in mice receiving green tea was significantly lower than in those receiving glyoxylate alone.Conclusions:RTC injury, especially mitochondrial damage, and oxidative stress induce the early stage of calcium oxalate crystal formation in mice.