目的 評價六味地黃丸對順鉑誘導的大鼠腎臟損傷模型的保護作用及其作用機制。方法 雄性Wistar大鼠隨機分為對照組、模型組、六味地黃丸（0.54、1.08 g/kg）組。注射用順鉑7.5 mg/kg單次腹腔注射建立模型，六味地黃丸ig 10 d。采用肌氨酸氧化酶法檢測各組血清中肌酐（Cr）、尿素氮（BUN）含量，采用WST-1法檢測腎組織中超氧化物歧化酶（SOD），采用化學比色法檢丙二醛（MDA）、谷胱甘肽過氧化物酶（GSH-Px）水平，采用ELISA方法檢測腎損傷因子-1（Kim-1）濃度。檢測腎組織中核轉(zhuǎn)錄因子E2相關(guān)因子2（Nrf2）、醌氧化還原酶1（NQO1）、血氧合酶1（HO-1）、Kelch樣環(huán)氧氯丙烷相關(guān)蛋白1（Keap1）的mRNA相對表達量。結(jié)果 六味地黃丸可減輕順鉑誘導的急性腎損傷大鼠腎小管損傷。六味地黃丸（0.54、1.08 g/kg）組腎臟系數(shù)顯著低于模型組（P<0.05）。予六味地黃丸后，Cr、BUN明顯低于模型組（P<0.05）。Kim-1值明顯降低（P<0.05）；SOD、GSH-Px活力顯著升高，MDA含量明顯下降（P<0.05）；Nrf2、NQO1、HO-1的mRNA相對表達量高于模型組，Keap-1的mRNA表達受到抑制，表達量低于模型組（P<0.05），且1.08 g/kg較0.54 g/kg差異更明顯（P<0.05）。結(jié)論 六味地黃丸對順鉑誘導的大鼠急性腎損傷有顯著的保護作用，其機制與激活Nrf2通路有關(guān)。

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.

天津中醫(yī)藥大學中西醫(yī)結(jié)合創(chuàng)新基金課題（CXJJLX201718）