Mitochondrial dysfunction in the process of cisplatin-induced acute kidney injury in mice
10.3760/cma.j.issn.1001-7097.2013.12.008
- VernacularTitle:线粒体功能障碍参与顺铂诱导的小鼠急性肾损伤
- Author:
Jingjing PAN
;
Xiaoyan XUAN
;
Aihua ZHANG
;
Guixia DING
- Publication Type:Journal Article
- Keywords:
Cisplatin;
Mitochondria;
Acute kidney injury;
Kidney injury molecule-1;
Mitochondrial dysfunction
- From:
Chinese Journal of Nephrology
2013;29(12):914-919
- CountryChina
- Language:Chinese
-
Abstract:
Objective To assess the characteristics of different doses of cisplatin-induced acute kidney injury,further to understand mitochondrial dysfunction and its role in acute kidney injury (AKI).Methods Male C57BL/6J mice were first randomly divided into two groups:control group (n =6) and AKI group (n =12).Then,AKI group was subsequently divided into other two groups according to different dose of cisplatin (10 mg/kg or 20 mg/kg).AKI group received intraperitoneal injection of cisplatin.All mice were sacrificed after 72 h of injection.Renal biochemical function,renal pathological changes,renal injury markers,kidney mitochondrial function and structural changes were observed.Results (1) After 72 hours of injection,the AKI group performed significant kidney injury changes compared to control group,thereinto 20 mg/kg group was more serious than 10 mg/kg group.With the cisplatin dose increasing,renal function markers such as serum creatinine,urine protein gradually increased.(2)Kidney biopsy showed tubular structural damage,the formation of protein casts,kidney injury molecule-1 (KIM-1) gradually increased(P ＜ 0.05).(3)Electron microscopy found tubular mitochondrial structural damage,mtDNA copy number decreased,the level of peroxisome proliferatoractivated receptor-gamma coactivator-1alpha (PGC-1α),ATP synthase β decreased(P ＜ 0.05),and Western blotting manifested cytochrome C was released from mitochondria to the cytoplasm.These data all exhibited significant difference between different groups(P ＜ 0.05).Conclusions Cisplatin induces acute kidney injury in dose-dependent manner.Mitochondrial dysfunction participates in kidney injury,and is also related to the kidney pathological damage.
