Soejima A, Suzuki M, Waku M, Kitamoto K, Nagasawa T
First Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Nihon Jinzo Gakkai Shi. 1992 Jun;34(6):677-81.
We investigated to confirm the biochemical mechanisms of the hypothesis that lipid peroxidation participates in the pathogenesis of aminoglycoside-induced nephrotoxicity. Male Sprague-Dawley rats were injected with gentamicin (GM), 300mg/kg per day. Twenty-four hours after the injection the rats were killed and the renal cortex was processed for glutathione (GSH), malondialdehyde (MDA), phospholipase A2 (PLA2), phosphatidylcholine (PC), sphingomyelin (SPH) and phospholipids (PL). And we also studied the GSH reduced rats by buthionine sulfoximine (BSO) administration, to compare the biochemical differences with these parameters in two groups. GM induced a significant decrease of PLA2, SHP/PC ratio and GSH. Marked elevation of MDA (lipid peroxidation) and PC were observed after a single injection of GM. In contrast, BSO injected rats were not showed increment of tissue MDA, in spite of marked reduction of renal GSH. These data support the conclusion that accelerated lipid peroxidation occurs early in the course of GM administration and inhibition of lysosomal PLA2 activity involved in the degradation of lysosomal membrane which consisted of phospholipids.
我们进行研究以证实脂质过氧化参与氨基糖苷类药物所致肾毒性发病机制这一假说的生化机制。将雄性Sprague-Dawley大鼠每日注射庆大霉素（GM），剂量为300mg/kg。注射后24小时处死大鼠，取肾皮质检测谷胱甘肽（GSH）、丙二醛（MDA）、磷脂酶A2（PLA2）、磷脂酰胆碱（PC）、鞘磷脂（SPH）和磷脂（PL）。我们还通过给予丁硫氨酸亚砜胺（BSO）使大鼠体内GSH减少，以比较两组这些参数的生化差异。GM导致PLA2、SHP/PC比值和GSH显著降低。单次注射GM后观察到MDA（脂质过氧化）和PC显著升高。相比之下，尽管肾GSH显著降低，但注射BSO的大鼠组织MDA并未增加。这些数据支持以下结论：在GM给药过程早期发生了加速的脂质过氧化，且溶酶体PLA2活性受到抑制，该酶参与由磷脂构成的溶酶体膜的降解。
