中文摘要：

目的通过观察顺铂在不同剂量下诱导小鼠急性。肾损伤的特点，进一步了解线粒体功能障碍参与急性肾损伤的机制。方法雄性C57BL／6J小鼠18只，随机分为正常对照组（／I=6）及顺铂处理组（n=12），其中顺铂处理组按顺铂给予剂量不同又分为10mg／kg组（／I=6）和20mg／kg组（n=6）。采用顺铂单次腹腔注射建立急性肾损伤模型，72h后处死小鼠。测定肾功能相关生化指标、肾组织病理改变、肾损伤标志物的变化以及肾脏线粒体功能及结构变化指标。结果（1）顺铂注射72h后，顺铂处理组与对照组相比出现明显急性肾损伤表现，其中20mg／kg组肾损伤程度更为严重，表现为随着顺铂剂量加大，肾生化指标血肌酐、尿蛋白等水平逐渐升高。（2）顺铂处理组肾小管结构破坏，蛋白管型形成，同时肾损伤标志物肾损伤分子1（KIM-1）mRNA升高（P〈0．05）。（3）顺铂处理组肾小管线粒体结构破坏明显，同时线粒体DNA拷贝数下降（P〈0．05），线粒体相关蛋白过氧化物酶体增殖活化受体1辅助活化因子1α（PGC—1α）及ATP合酶表达降低（P〈0．01），细胞色素C从线粒体向胞质释放；且不同浓度顺铂组间各项指标差异亦有统计学意义（P〈0．05）。结论顺铂能够呈剂量依赖性的诱导急性肾损伤发生，线粒体功能障碍参与了肾损伤发生，并与肾损伤的病理改变密切相关。

英文摘要：

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 inereased（P 〈 0.05）. （3）Electron microscopy found tubular mitochondrial structural damage, mtDNA copy number decreased, the level of peroxisome proliferator-activated receptor -gamma coactivator-lalpha （PGC- lc0, ATP synthase 13 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.