大剂量顺铂所致大鼠急性肾损害过程中血浆内皮素-1与肾功能变化的关系

Significance of blood endothelin-1 in acute renal failure induced by high-dose cisplatin in rats

[目的]研究大剂量顺铂(cisplatin,DDP)所致大鼠急性肾功能衰竭过程中血浆内皮素(ET-1)与肾功能变化的关系。[方法]SD大鼠24只,依体重随机分为DDP用药后3、6、48 h组和NS对照组,每组6只。10 mg/kgDDP单次腹腔内注射,等量生理盐水对照。随后观察并记录用药后大鼠的体重、血浆尿素氮和肌酐浓度、血浆ET-1含量、肾系数等变化。[结果]大剂量DDP用药后6 h大鼠体重明显降低;用药后48 h大鼠血浆尿素氮(BUN)和肌酐(Cre)明显高于对照组(P<0.05),出现肾功能衰竭;用药后72 h 66%的大鼠死亡。大剂量DDP用药后6 h,大鼠肾系数为11.3±1.2,与对照组9.0±0.8比较差异有显著性意义(P<0.05)。大剂量DDP用药后3 h大鼠血浆ET-1升至(213.68±28.3)ng/mL,与对照组(157.45±27.7)ng/mL比较差异具有显著性意义(P<0.01),DDP用药72 h后存活大鼠血浆ET-1亦明显高于对照组(P<0.05)。[结论]大剂量DDP所致的急性肾功能衰竭与血浆ET-1浓度的变化有关,但大鼠肾功能的变化与血浆ET-1的变化不一致,提示ET-1可能在DDP所致肾毒性损伤早期的发病机制中发挥重要作用。

[ Objective ] To study the relationship between plasma endothelin - 1 （ ET - 1 ） and renal function in acute renal failure induced by high -dose cisplatin （DDP） in rats. [ Methods] SD rats 24 were divided randomly into 4 groups： 3,6, 48 h after DDP administration group and control group （n =6 in each group）. DDP （10 mg/kg） was injected intraperitoneally and the same volume of natural saline was given as control. Body weight was measured subsequently and blood samples were obtained. Renal coefficient was measured and blood urea nitrogen （BUN） and creatinine （Cre） were measured by the automatic biochemistry analyzer. Plasma ET - 1 was measured by radioimmunoassay. [ Results ] Body weight of rats decreased significantly at 6 h after DDP administration. Compared with control, blood BUN and Cre increased significantly in rats 48 h after administrations （P 〈 0.01 ） and 66% of rats died of acute renal failure 72 h after DDP administration.The renal coefficients is 11.3 ± 1.2 at 6 h after DDP administrations, significantly higher than that 9.0 ± 0.8 in control group （P 〈 0.05 ）. Plasma ET - 1 increased to （213.68 ± 28.3 ） ng/mL 3 hours after DDP administration, significantly higher than that （157.45 ± 27.7）ng/mL in control group （P 〈 0.01 ）. Then it decreased a little but sustained in a higher level （P 〈 0.05）. Plasma ET - 1 was remarkably higher in survival rats 72 h after DDP administration than in control （P 〈0.05）. [ Conclusion] The changes of plasma ET- 1 is related to acute renal failure induced by high -dose DDP. Although there was no positive correlation between plasma ET - 1 and renal function, early and quickly increase of plasma ET - 1 may be an important pathophysiological mechanism of cisplatin - induced nephrotoxicity.