中文摘要：

目的探讨庆大霉素肾毒性损伤能否诱导一种新的肾间质纤维化模型。方法31只健康雄性Wister大鼠随机分为4组：正常组I、模型组I（造模后5d取材）组；正常组Ⅱ、模型组Ⅱ（造模后30d取材）组。给予庆大霉素造成肾毒性损伤，分别于造模后5d和造模后30d处死，光镜和电镜下动态观察肾组织形态学改变，计算肾系数、检测血肌酐、血尿素氮、24小时尿蛋白总量，氧化应激相关指标SOD、MDA、NOS的变化，检测NF-kB蛋白表达水平。结果（1）模型组Ⅰ大鼠：光镜下可见肾小管上皮细胞以变性为主，部分坏死；有较多的蛋白管型和少量的细胞管型、颗粒管型。电镜下可见肾小管上皮细胞胞浆中有大量脂滴存在，细胞的线粒体肿胀、内质网明显扩张。肾系数常、血肌酐、血尿素氮、24h尿蛋白总量，以及MDA、NOS明显高于正常组I（P〈0．01），模型组INF-kB蛋白表达水平明显高于正常组Ⅰ（P〈0．01）；SOD明显低于正常组Ⅰ（P〈0．01）。（2）模型组Ⅱ大鼠：肾小管上皮细胞以坏死为主，部分上皮细胞变性，可见肾小管萎缩和扩张，有较多的细胞管型和颗粒管型，间质中有成纤维细胞增生和炎症细胞浸润，间质明显增宽。电镜下可见模型组Ⅱ大鼠肾小管上皮细胞核固缩、碎裂现象；间质中有较多的胶原纤维，成纤维细胞增多。模型组Ⅱ大鼠血肌酐、血尿素氮、24h尿蛋白总量明显高于正常组Ⅱ（P〈0．01）。结论氧化应激引起的脂质过氧化损伤参与了庆大霉素所致的肾小管上皮细胞变性坏死，后者导致了慢性炎症和修复的反复进行，最终导致肾间质纤维化。

英文摘要：

Objective To investigate the possibility of a novel model of renal interstitial fibrosis induced by renal toxic injury caused by gentamicin. Methods 31 healthy female Wister rats were randomized into 4 groups： the normal group I, the model I group（executed 5 days after modeling） ;the normal group Ⅱ , model group Ⅱ（executed 30 days after modeling）. The renal interstitial fibrosis in rats was induced by gentamicin. The rats were executed 5 or 30 days after modeling, respectively. Under the light microscope and electron microscope, the changes of renal histomorphology were dynamically observed. The renal indexes were calculated and the changes of serum creatinine, blood urea nitrogen, total urinary protein in 24 h, and oxidative stress-related indexes such as SOD, MDA and NOS were detected, and the level of NF-kB was detected. Results （ 1 ） Rats in the model Ⅰ group： under the light microscope, it was observed that there was mainly degeneration and partly necrosis in the renal tubular epithelial cells; there were also many protein casts and a few cellular casts and granular casts. Under the electron microscope, there were a large amount of lipid droplets in the kytoplasm of renal tubular epithelial cell, swollen cellular bioblasts, and apparent expansion of endoplasmic reticulum. The renal indexes, serum creatinine, blood urea nitrogen, total urinary protein in 24 h, MDA and NOS were significantly higher than those in the normal group Ⅰ（ P 〈 0.01 ） ;While SOD was significantly lower than that in the normal group I（ P 〈 0.01 ）. The level of NF-kB in model group was higher than the normol group I significantly（ P 〈 0.01 ）. （2） Rats in the model Ⅱ group： Under the light microscope, it was observed that there was mainly necrosis and partly degeneration in the renal tubular epithelial cells, atrophy and expansion of the renal tubule, many cellular casts and granular casts, and proliferation of fibroblasts and infiltration of the inflammatory cells in the interstitial sub