Inhibition of Mitochondrial Complex I Aggravates Folic Acid-Induced Acute Kidney Injury
Inhibition of Mitochondrial Complex I Aggravates Folic Acid-Induced Acute Kidney Injury
复制标题
抑制线粒体复合物 I 会加重叶酸引起的急性肾损伤
DOI：
10.1159/000501934
复制
发表时间：
2019-09
影响因子：
2.8
通讯作者：
Huang Songming
中科院分区：
文献类型：
--
作者：
Zhang Wen;Yang Yunwen;Gao Huiping;Zhang Yue;Jia Zhanjun;Huang Songming
研究背景：线粒体功能障碍与多种肾脏损伤有关。然而，线粒体功能障碍在急性肾损伤（阿基）发病机制中的作用仍需证据。方法：我们评估线粒体复合物I抑制剂鱼藤酮对叶酸（FA）诱导的小鼠阿基的影响。结果如下：引人注目的是，与单独的FA组相比，用食物中200 ppm剂量的鱼藤酮预处理的小鼠显示出加重的肾损伤，如通过更高水平的血尿素氮和肌酐所示。同时，鱼藤酮预处理小鼠肾小管损伤评分和肾小管损伤标志物中性粒细胞明胶酶相关脂质运载蛋白表达进一步升高，提示肾小管损伤加重。此外，鱼藤酮预处理组小鼠肾脏线粒体DNA拷贝数减少，线粒体细胞色素c氧化酶亚单位1、线粒体NADH脱氢酶亚单位1和线粒体特异性超氧化物歧化酶（SOD 2）表达进一步降低，提示线粒体损伤加重。与SOD 2减少平行，氧化应激标志物丙二醛和HO-1在鱼藤酮预处理的阿基小鼠中显示出更大的增量，与恶化的凋亡反应和炎症一致。结论：我们的研究结果表明，线粒体复合物I活性的抑制加重了肾小管损伤，线粒体损伤，氧化应激，细胞凋亡和炎症在FA诱导的阿基。
Background: Some researches revealed that mitochondrial dysfunction is associated with various kidney injury. However, the role of mitochondrial dysfunction in the pathogenesis of acute kidney injury (AKI) still needs evidence. Methods: We evaluated the effect of mitochondrial complex I inhibitor rotenone on folic acid (FA)-induced AKI in mice. Results: Strikingly, the mice pretreated with rotenone at a dose of 200 ppm in food showed exacerbated kidney injury as shown by higher levels of blood urea nitrogen and creatinine compared with FA alone group. Meanwhile, both renal tubular injury score and the expression of renal tubular injury marker neutrophil gelatinase-associated lipocalin were further elevated in rotenone-pretreated mice, suggesting the deteriorated renal tubular injury. Moreover, the decrements of mitochondrial DNA copy number and the expressions of mitochondrial Cytochrome c oxidase subunit 1, mitochondrial NADH dehydrogenase subunit 1, and mitochondria-specific superoxide dismutase (SOD2) in the kidneys of FA-treated mice were further reduced in rotenone-pretreated mice, indicating the aggravated mitochondrial damage. In parallel with the SOD2 reduction, the oxidative stress markers of malondialdehyde and HO-1 displayed greater increment in AKI mice with rotenone pretreatment in line with the deteriorated apoptotic response and inflammation. Conclusion: Our results suggested that the inhibition of mitochondrial complex I activity aggravated renal tubular injury, mitochondrial damage, oxidative stress, cell apoptosis, and inflammation in FA-induced AKI.
登录
查看更多内容
DOI：
10.1016/b978-1-4160-4252-5.50014-9
发表时间：
2021-02
期刊：
BMJ clinical evidence
影响因子：
--
作者：
J. Kellum;M. Unruh;R. Murugan
通讯作者：
J. Kellum;M. Unruh;R. Murugan
影响因子：
13.6
作者：
Kielar, ML;John, R;Lu, CY
通讯作者：
Lu, CY
DOI：
10.1007/978-3-319-11020-2_41
发表时间：
2015
期刊：
Goldman's Cecil Medicine
影响因子：
--
作者：
P. Marik
通讯作者：
P. Marik
改善线粒体功能是吡非尼酮对 5/6 肾切除大鼠肾小管间质纤维化的保护作用的基础
影响因子：
3.7
作者：
Chen JF;Liu H;Ni HF;Lv LL;Zhang MH;Zhang AH;Tang RN;Chen PS;Liu BC
通讯作者：
Liu BC
DOI：
10.1159/isbn.978-3-318-01456-3
发表时间：
2014-02
期刊：
--
影响因子：
--
作者：
S. Demirjian;J. Nally
通讯作者：
S. Demirjian;J. Nally