健脾养正消癥方通过激活PI3K/AKT信号通路减轻顺铂所致的肾毒性作用  

Effect of Jianpi Yangzheng Xiaozheng Formula in Attenuating Cisplatin-induced Nephrotoxicity by Activating PI3K/AKT Signal Pathway

作　　者：吴坚[1] 邹玺[1] 刘沈林[1] 陈敏[1] 张星星[1] 

机构地区：[1]南京中医药大学附属医院,南京210029

出　　处：《中国实验方剂学杂志》2015年第17期106-110,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家中医药管理局项目(JDZX2012086);国家自然科学基金面上项目(81473605);江苏省临床医学科技专项(BL2014100)

摘　　要：目的:探讨健脾养正消癥方对顺铂肾毒性的防护作用及可能机制。方法:40只BALB/C小鼠,随机分为荷瘤组,顺铂组,健脾养正消癥方组,健脾养正消癥方和顺铂(联合用药)组,每组10只,按组别ig给药5 d后,将BALB/C小鼠右腋下注射H22腹水瘤,形成荷瘤小鼠模型并一次性注射顺铂20 mg·kg-1造成肾损害。造模后10 d,观察小鼠肾脏指数,血肌酐(SCr),血尿素氮(BUN),肾组织病理变化;并通过TUNEL,Western blot法检测健脾养正消癥方对顺铂损伤小鼠肾组织中凋亡及PI3K/AKT信号通路相关分子蛋白表达的影响。结果:与荷瘤组比较,顺铂组小鼠肾脏系数,SCr,BUN显著升高(P<0.05),肾脏病理损伤明显,肾小管凋亡细胞增多,肾组织p-PI3K,p-AKT表达下调,Caspase-3表达上调(P<0.05);与顺铂组比较,联合用药组肾脏指数降低,SCr,BUN下降(P<0.05),肾脏病理损害减轻,肾小管凋亡细胞减少,肾组织p-PI3K,p-AKT表达上调,Caspase-3表达下调(P<0.05)。结论:健脾养正消癥方能明显减轻顺铂引起的肾毒性,其作用机制与激活PI3K/AKT信号通路,减少细胞凋亡有关。Objective： To study the protective effect of Jianpi Yangzheng Xiaozheng formula（ JPYZXZF） on nephrotoxicity induced by cisplatin（ CP） in mice and its possible mechanism. Method： Totally40 BALB / c mice were randomly divided into 4 groups： the tumor-bearing group,the CP group,the JPYZXZF group and the CP ＋ JPYZXZF group,with 10 mice in each group. Each group was orally given drugs for five days.BALB / c mice were injected with H22 cells to establish the tumor-bearing mice model and 20 mg·kg- 1cisplatin for one time to cause kidney damage. On the 10 thday after the modeling,kidney index,blood urea nitrogen（ BUN）,serum creatinine（ SCr） and kidney pathological changes were observed. The apoptosis of renal tissues of the mice and relevant protein expressions of PI3 K / AKT signal pathway were examined by TUNEL and Western blot. Result：Compared with the tumor-bearing group,kidney indexes,SCr and BUN were significant increased in the CP group（ P〈0. 05）,with increase in apoptotic cells at renal tubules,down-regulation in the protein expressions of p-PI3 K,p-AKT in renal tissues and up-regulation in Caspase-3 expression（ P〈0. 05）. Compared with the CP group,the CP ＋ JPYZXZF group showed reduction in kidney indexes,SCr and BUN（ P〈0. 05）,damages of renal tissues and apoptotic cells at renal tubules,up-regulation in the protein expressions of p-PI3 K,p-AKT in renal tissues and down-regulation in Caspase-3 expression（ P〈0. 05）. Conclusion： JPYZXZF can reduce the nephrotoxicity caused by CP. Its mechanism is ccorelated with the activation of PI3 K / AKT signal pathway and the decrease in the protein expression of Caspase-3.

关 键 词：健脾养正消癥方 顺铂 肾毒性 凋亡 PI3K/AKT 

分 类 号：R285.5[医药卫生—中药学]