大剂量顺铂所致大鼠急性肾损害过程中内源性血管活性物质的动态变化及其意义

Significance of changes of blood nitric oxide and endothelin-1 levels in rats with acute renal failure induced by high-dose cisplatin

关键词:  大剂量顺铂  急性肾功能衰竭  血浆内皮素  血浆一氧化氮  大鼠

Key words:  cisplatin (DDP)  acute renal failure  nitric oxide (NO)  endothelin -1 (ET-1)  rats

摘要:

［目的］观察内源性血管活性物质内皮素（ET-1）和一氧化氮(NO)在大剂量顺铂（DDP）所致大鼠急性肾损害过程中的动态变化及其意义。［方法］SD大鼠24只，雌雄各半，依体重随机分组，DDP用药组18只和NS对照组6只。10 mg/kg DDP单次腹腔内注射，等量生理盐水对照。DDP用药前和DDP用药后3、6、48 h分别取大鼠6只，称重后内眦静脉取血，放射免疫法测定血浆ET-1水平，比色法测定血浆NO含量，统计学分析。 ［结果］大剂量DDP用药后3 h大鼠血ET-1升至（213.68±28.3）ng/mL，与对照组大鼠（157.45 ± 27.7）ng/mL比较差异具有显著性意义（P<0.01）。用药后6 h血浆ET-1较前稍下降，随后持续在较高水平，与对照组比较差异仍有显著性意义（P<0.05）。大剂量DDP用药后3 h，大鼠血浆NO含量开始升高，用药后6 h升至（166.67±84.62）μmol/L，与对照组大鼠（32.85±12.98）μmol/L比较，差异具显著性意义（P<0.01）；用药后48 h 血NO较前稍微下降，但与对照组比较差异仍具有显著性意义（P<0.01）。［结论］血浆ET-1和NO浓度的变化与大剂量顺铂所致急性肾功能衰竭有关，二者可能在顺铂所致肾毒性损伤早期的发病机制中发挥重要作用。

Abstract:

［Objective］To observe the dynamic changes of blood nitric oxide (NO) and endothelin -1 (ET-1) in rats with acute renal failure induced by high-dose cisplatin (DDP).［Methods］24 SD rats were divided randomly into DDP group and control group according to weight. DDP (10mg/kg) were injected intraperitoneally and the same volume of natural saline was given as control. Blood samples were obtained from orbital venous sinus before and 3 h, 6 h, 48 h after DDP administration, and then plasma ET-1 was measured by using radioimmunoassay, while plasma NO was examined with nitrite reduction test.［Results］Plasma ET-1 was (213.68 ± 28.3) ng/mL at 3 hours after DDP administration, significantly higher than that (157.45±27.7) ng/mL in control group (P<0.01). It decreased a little in 6 hours after DDP administration, and then sustained in a higher level. There is significant difference compared with control group (P<0.05). Plasma NO started to rise in 3 hours after DDP administration. It increased to (166.67±84.62) μmol/L in 6 hours after DDP administration, significantly higher than that (32.85±12.98) μmol/L in control group (P<0.01). Then it decreased a little at 48 hours after DDP administration, but still higher than that of control group (P<0.01).［Conclusion］The changes of plasma ET-1 and NO concentration are related to acute renal failure induced by high-dose cisplatin. Plasma ET-1 and NO probably play an important role in the early stage of the pathogenesis of cisplatin-induced nephrotoxicity.