一氧化氮在顺铂致大鼠肾损害过程中的作用

Role of nitric oxide in cisplatin induced kidney damage in rats

【目的】 探讨一氧化氮在顺铂肾毒性氧化应激机制中的作用。【方法】 采用少量多次给大鼠腹腔注射顺铂 (CP)及经口给予水飞蓟素 (SB)预处理后给予CP模型 ,观察血尿素氮 (BUN)含量、一氧化氮 (NO)含量、一氧化氮合酶 (NOS)活性、丙二醛 (MDA)形成、超氧化物歧化酶 (SOD)活性等指标的变化。【结果】 CP可诱导NOS活性增高 ,使NO生成量增多 ;BUN含量与MDA含量及SOD活性的变化并不完全一致 ,而与NO含量的时相变化趋势基本一致 ;SB可使BUN含量、MDA含量及NO含量降至对照组水平 ,同时可使SOD活性明显升高。【结论】 NO可能在CP所致肾损害中起更重要的作用 ,SB可预防CP所致的肾损害 ,其机制可能与SB降低NO生成量。

Objective To explore the role of nitric oxide in oxidative stress mechanisms in cisplatin induced kidney damage in rats. Methods Fifty four rats were randomly divided into three groups of 18 rats each.The three groups were given normal saline,CP(1 mg/kg/day) intraperitoneally or SB(24 mg/kg/day) orally,1 hour prior to CP,respectively.Having been treated daily for 7 days,six animals of each group were killed at day 2,day 5 or day 10 after the last administration.The indicators included the level of blood urea nitrogen (BUN),the formation of malondialdehyde (MDA),Nitric oxide (NO) content,the activity of superoxide dismutase (SOD),the histochemical change of nitric oxide synthase (NOS),etc. Results The results showed that the increase of the productions of NO by increasing the activities of NOS was more related to the nephrotoxicity induced by CP than the decrease of the activities of SOD and the increase of MDA contents related.The pretreatment of SB could ameliorate the nephrotoxicity induced by CP,and the possible mechanism was related to decrease NO production and to increase activity of SOD. Conclusion NO maybe play an important role in nephrotoxicity induced by CP.