摘要
为了探讨庆大霉素(GM)肾毒性的发病机理,我们观察了单次ip GM 100 mg/kg或100 mg·kg^(-1)·d^(-1)共3 d的家兔血浆肌酐浓度(PCr,μmol/L)、肌酐清除率(CCr,ml·kg^(-1)·h^(-1)、尿蛋白定性记分(UP)、肾皮质脂质过氧化物含量(LPO,μmol/g蛋白)和肾皮质钠钾ATP酶活性(mmol磷·g蛋白(?)·min^(-1))的变化,以及电镜下肾小球内皮细胞、足细胞和近端肾小管上皮细胞的超微结构变化。以等容积生理盐水ip为对照组。发现家兔单次ip GM后24 h,PCr增高到114±SD 17(对照组76±SD 15,p<0.05);CCr降到82±SD 23(对照组(133±SD 19,p<0.05);UP增高到1.10±SD0.11(对照组0.05±SD 0.01,p<0.001);LPO增高到0.68±SD 0.19(对照组0.48±SD 0.16,p<0.05);肾皮质钠钾ATP酶活性降到0.053±SD0.012(对照组0.071±SD 0.017,p<0.05);肾皮质钠钾ATP酶活性与LPO含量呈显著负相关,LPO越高,钠钾ATP酶活性越低;组织学上,肾小球内皮细胞和足细胞有明显的肿胀变性,肾小球毛细血管腔变窄,近端肾小管上皮细胞内出现大量髓样小体,大部分髓样小体位于溶酶体内,少数位于变性肿胀的线粒体内或与变性内质网相接,可见溶酶体吞噬髓样小体的现象。家兔ip3次GM后24 h,肾功能损害更重;组织学上,肾小球内皮细胞和足细胞肿胀更显著,核有改变。
In order to clarify the mechanism of gentamicin(GM) nephrotoxicity, plasma creatinine level (PCr), clearance of creatinine (CCr), qualitative grade of urine protein(UP), renal cortex lipid peroxides content (LPO) and renal cortex Na+, K+-ATPase activity were determined, and the ultrastructural changes of the renal cortex were observed in rabbits receiving a single injection of 100 mg / kg GM or one dose of GM injection per day for 3 d. The other rabbits were given a single injection of 1 ml / kg saline or on dose of saline injection per day for 3 d to serve as the control.It was found that 24 h after a sigle injection of GM, there were a significant increase of PCr, UP, and LPO, and a significant decrease of CCr, and Na+, K+-ATPase activity as compared with those of the control. The Na+, K+-ATPase activity in the renal cortex had a negative correlation with the renal cortex LPO content. The glomerular endothelial cells and podocytes, and the epithelial cells of the proximal tubules showed obvious histological lesions. The functional and morphological damages of the renal glomeruli and proximal tubules became rather severe 24 h after the third injection of GM.It was concluded that there were marked glomerular damages as well as damages on the proximal tubules after intraperitoneal injection of GM, and these damages might be mediated through free radicals.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
1991年第3期209-213,共5页
Chinese Journal of Pharmacology and Toxicology
关键词
庆大霉素
肾小球损伤
肾毒性
兔
gentamicin
rabbits
nephrotoxi-city
lipid peroxide
Na+, K+-ATPase
