黄芪注射液对顺铂所致小鼠肾损害的保护作用

Astragalus injection ameliorates cisplatin-induced nephrotoxicity in mice

目的:观察黄芪注射液(AI)对顺铂(DDP)化疗模型小鼠肾脏损害的保护作用,并探讨其作用机制。方法:建立小鼠S180移植瘤模型,随机分为5组,即对照组(生理盐水)、DDP组(3.5 mg.kg-1)、AI(12,8,4 g.kg-1)干预组,剥离皮下肿瘤称重计算抑瘤率,血清标本检测尿素氮(BUN)、肌酐(CR),取肾组织称重计算肾脏系数,病理切片观察肾组织形态学改变,原位缺口末端标记法(TUNEL)检测凋亡细胞,免疫组化检测Bax,Bcl-2蛋白表达。结果:与对照组比较,DDP及AI各干预组抑瘤率均显著提高(P<0.05);中、高剂量AI干预组还可提高DDP抑瘤率(P<0.05)。与对照组比较,DDP组调亡细胞数及Bax/Bcl-2均明显增加(P<0.05);与DDP组比较,AI高剂量干预组调亡细胞数及Bax/Bcl-2均显著下降(P<0.05),中、低剂量干预组效果不明显;各AI干预组动物肾功能损害及肾组织病理改变均得到明显改善。结论:AI能在不影响DDP抗瘤作用前提下防护DDP所致小鼠肾损害,其机制可能与调节肾组织Bax,Bcl-2的蛋白表达有关。

Objective： To examine the protective effects of Astragalus injection（AI） on cisplatin（DDP）-induced nephrotoxicity and to explore the mechanism of its nephroprotection.Method： The S180-bearing model was established,and fifty mice were randomly divided into five groups： control mice,DDP-injected mice（3.5 mg·kg^-1and AI-pretreated mice（12,8,4 g·kg^-1）.Tumor inhibition rate,renal functions,histological findings were investigated.The apoptotic cells were counted by TUNEL and the presence of Bax,Bcl-2 in renal tissues was determined by immunohistochemistry.Result： Administration of DDP or DDP plus AI showed promising anti-tumor activities as compared with control group.Interestingly,a combination of DDP and AI（12,8 g·kg^-1）led to enhanced tumor growth inhibition as compared with DDP alone（all P〈0.05）.Compared with that from control,the number of TUNEL-positive cells and the Bax/Bcl-2 ratio was increased significantly in the kidneys of DDP treated mice（P〈0.05）.High-dose AI pretreatment significantly reduced the elevated number of TUNEL-positive cells and the Bax/Bcl-2 ratio（P〈0.05）,and it showed a superior nephroprotective effect than any other dose.AI significantly also decreased both the damage to renal function and histological pathology.Conclusion： Pre-treatment with AI attenuates cisplatin-induced nephrotoxicity without compromising the anti-tumor efficacy of DDP,which might be invovlved in regulating the Bax and Bcl-2 expression.