目的 评价六味地黄丸对顺铂诱导的大鼠肾脏损伤模型的保护作用及其作用机制。方法 雄性Wistar大鼠随机分为对照组、模型组、六味地黄丸（0.54、1.08 g/kg）组。注射用顺铂7.5 mg/kg单次腹腔注射建立模型，六味地黄丸ig 10 d。采用肌氨酸氧化酶法检测各组血清中肌酐（Cr）、尿素氮（BUN）含量，采用WST-1法检测肾组织中超氧化物歧化酶（SOD），采用化学比色法检丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）水平，采用ELISA方法检测肾损伤因子-1（Kim-1）浓度。检测肾组织中核转录因子E2相关因子2（Nrf2）、醌氧化还原酶1（NQO1）、血氧合酶1（HO-1）、Kelch样环氧氯丙烷相关蛋白1（Keap1）的mRNA相对表达量。结果 六味地黄丸可减轻顺铂诱导的急性肾损伤大鼠肾小管损伤。六味地黄丸（0.54、1.08 g/kg）组肾脏系数显著低于模型组（P<0.05）。予六味地黄丸后，Cr、BUN明显低于模型组（P<0.05）。Kim-1值明显降低（P<0.05）；SOD、GSH-Px活力显著升高，MDA含量明显下降（P<0.05）；Nrf2、NQO1、HO-1的mRNA相对表达量高于模型组，Keap-1的mRNA表达受到抑制，表达量低于模型组（P<0.05），且1.08 g/kg较0.54 g/kg差异更明显（P<0.05）。结论 六味地黄丸对顺铂诱导的大鼠急性肾损伤有显著的保护作用，其机制与激活Nrf2通路有关。

Objective To evaluate the protective effect of Liuwei Dihuang Pills on cisplatin-induced acute kidney injury in rats. Methods Male Wistar rats were randomly divided into control group, model group, and Liuwei Dihuang Pills (0.54 and 1.08 g/kg) groups. Rats were ip administered with Cisplatin for Injection 7.5 mg/kg to establish model, and ig administered with Liuwei Dihuang Pills for 10 d. Cr and BUN was determined by sarcosine oxidase method. The levels of SOD were detected by WST-1 method. MDA and GSH-Px were detected by chemical colorimetry. The concentrations were detected by ELISA. And the relative expressions of mRNA of Nrf2, NQO1, HO-1, and Keap1 in renal tissue were detected. Results Liuwei Dihuang Pills could significantly decrease the renal tubule injury induced by cisplatin in rats with acute renal injury. The kidney coefficient in the Liuwei Dihuang Pills groups (0.54 and 1.08 g/kg) were significantly lower than that in the model group (P<0.05). After treated by Liuwei Dihuang Pills, Cr and BUN were significantly lower than those in the model group (P<0.05). After Liuwei Dihuang Pills was given, Kim-1 were significantly were decreased, but SOD and GSH- Px activity were significantly increased, and the MDA content was significantly decreased (P<0.05). The mRNA expression levels of Nrf2, NQO1 and ho-1 were higher than those in the model group, but the mRNA expression levels of keap-1 were inhibited, and the mRNA expression levels were lower than those in the model group (P<0.05), and the difference between high dose and low dose was more obvious. Conclusion Liuwei Dihuang Pills has a significant protective effect on cisplatin-induced acute kidney injury in rats, and its mechanism is related to activation of Nrf2 pathway.

天津中医药大学中西医结合创新基金课题（CXJJLX201718）