银杏黄酮对卡铂所致大鼠肾氧化损伤的保护作用及其机制

PREVENTION OF GINKGETIN AGAINST RENAL DAMAGE INDUCED BY CARBOPLATIN IN RATS

目的研究银杏黄酮(GBE)对卡铂(CBDCA)所致大鼠肾氧化损伤的保护作用,并探讨其可能机制。方法灌胃给予大鼠GBE后腹腔内注射CBDCA,5 d后检测肾脏、血清的氧化损伤指标,并测定尿与肾皮质中铂含量,观察GBE保护作用的剂量效应关系和时间效应关系。结果CBDCA组肾脏系数、NAG活性、BUN质量浓度分别为0.96×10-2g/g、23.58 U/g和87.05 mg/dL,均明显高于对照组(0.73×10-2g/g、14.08 U/g、22.55 mg/dL),P<0.01。250、500和750 mg/kgGBE预处理后第5天,大鼠肾脏系数、NAG活性和BUN质量浓度均不同程度减少,以500 mg/kg组GBE预处理的效果最明显,该组肾脏系数、NAG活性和BUN质量浓度分别为0.79×10-2g/g、15.86 U/g和25.98 mg/dL,明显低于CBDA组(P<0.05,P<0.01)。GBE预处理可抑制CBDCA引起的MDA形成增高,抑制GSH和GSH-Px活性下降,并能降低CBDCA所致大鼠肾皮质铂含量增高,促进铂经尿排泄。结论GBE对CBDCA的肾氧化损伤有保护作用,其部分机制为抗氧化作用,还可能与促进铂清除有关。

Objective To study the effect and mechanism of Ginkgetin （GBE） on prevention against carboplatin（CBDCA） induced-damage in rat. Methods After intragastric administration of GBE to rats, CBDCA was injected into abdominal cavity. Five days later rats were killed to detect the oxidative index in kidney, and senun. Content of platinum in urine, and renal cortex was measured, and the dose-dependent, and time-dependent relations were observed. Results After 5 days of pretreatmet with GBE of 250, 500 and 750mg/kg respectively, renal coefficient, activity of NAG and content of BUN were less than those in CBDCA group, particularly in GBE 500 mg/kg group, in which the renal coefficient was 0.79 × 10^-2g/g, activity of NAG 15.86 U/g Cre, and content of BUN 25.98 mg/dL whereas those in GBDCA group were 0.96 × 10^-2g/g, 23.58 U/g Cre, 87.05 mg/dL respectiely （ P 〈 0.05 or 0.01 ）. GBE pretreatment could reduce MDA and GSH content, and inhibit activity of GSH - Px, decrease cortical platinum content, and promote excretion of platinum from urine. Conclusion GBE has obvious effect of prevention from CBDCA nephrotoxicity, partially due to antioxidation and promoting clearance of platinum.