绿茶多酚对顺铂所致大鼠肾毒性的防护作用

Preventive Effects of Green Tea Polyphenols on Cisplatin-Induced Nephrotoxicity in Rats

[目的 ]研究绿茶多酚 (GTP)对顺铂 (CP)肾毒性的防护作用 ,并探讨其可能机制。 [方法 ]灌胃给予大鼠GTP后腹腔内注射CP ,检测肾脏系数、血清尿素氮 (BUN)及尿N 乙酰 β D 氨基葡萄糖苷酶 (NAG)、血还原型谷胱甘肽 (GSH)与肾皮质丙二醛 (MDA)及线粒体谷胱甘肽过氧化酶 (GSH Px)及尿与肾皮质铂含量 ,观察GTP的防护作用的剂量依赖关系和经时过程。 [结果 ] 2 5 0、5 0 0和 75 0mg/kgGTP预处理后第 5天 ,CP所致大鼠肾脏系数、NAG活性和BUN含量增高均不同程度减轻 ;5 0 0mg/kg组GTP预处理的效果最明显 ,该组肾脏系数、NAG活性和BUN含量分别为 ( 0 79± 0 12 )g/10 0g、( 15 86± 3 2 8)U/gCre和 ( 9 2 7± 3 77)mmol/L ,而CP组这 3项指标分别为 ( 0 96± 0 2 2 )g/10 0g、( 2 3 5 8± 5 45 )U/gCre和 ( 3 1 0 8± 15 0 0 )mmol/L ,上述各项指标两组间的差异有显著性 (P <0 0 5或 0 0 1)。GTP预处理可抑制CP引起的MDA形成增高 ,GSH含量和GSH Px活性下降 ,并能降低CP所致大鼠肾皮质铂含量增高 ,促进铂经尿排泄。 [结论 ]GTP有明显预防CP的肾毒性 ,其部分机制为抗氧化作用 ,还可能与促进铂清除有关。

Objective] To test the preventive effects of green tea polyphenols(GTP) on cisplatin induced nephrotoxicity and possible mechanisms in rats. [Methods] Rats were given orally GTP at 2 h prior to intraperitoneal injection of cisplatin. Kidney relative weight,blood urea nitrogen(BUN),urinary N acety1 β D glucosaminidase(NAG),glutathione(GSH) in blood,malondialdehyde(MDA) in kidney cortex homogemate,glutathione peroxidase(GSH Px) in mitochondria and Pt contents in urine and kidney cortex homogenate were detected. Dose dependent relationship and time course of the preventive effect of GTP on cisplatin induced nephrotxicity were observed . [Results] Pretreatment of GTP (250,500 and 750 mg/kg) could ameliorate increased kidney relative weight,BUN and urinary NAG induced by CP,and the efficacy of pretreatment with GTP at 500 mg/kg was the most significant. In this group,on 5 th day after pretreatment,the kidney relative weights,BUN and urinary NAG were (0 79±0 12)g/100 g,(15 86±3 28)U/g Cre and (9 27±3 77)mmol/L respectively,while in CP group the kidney relative weights,BUN and urinary NAG were (0 96±0 22)g/100 g、(23 58±5 45)U/g Cre and (31 08±15 00)mmol/L respectively,and the differences in the 3 indexes between groups pretreated with GTP at 500 mg/kg group and CP group were statistically significant ( P <0 05 or 0 01). Pretreatment with GTP could prevent the increase of MDA and decrease of GSH and GSH Px,and promote elimination of Pt. [Conclusion] It is evident that GTP can prevent cisplatin induced nephrotoxicity . Antioxidation is partly responsible for the prevention of GTP.