双环醇对顺铂联合吉西他滨致荷瘤小鼠肝肾损伤的保护作用

摘要

Objective To determine the effect of bicyclol on cisplatin plus gemcitabine induced liver and kidney injury in tumor-bearing mice. Methods C57/BL mice implanted with Lewis lung tumors for 6 days were treated with cisplatin (5mg·kg-1×5) and gemcitabine(50mg·kg-1×2) to establish the liver damage model. Bicyclol(150, 300mg·kg-1) was pretreated 1h before the injection of cisplatin/gemcitabine while rhG-CSF was setted as the positive control. All animals were killed on the sixth day after cisplatin/gemcitabine treatment starting. We used automatic biochemistry analyzer and the automatic blood analyzer to detect kinds of blood indicators about liver, renal and bone marrow functions. Results The combination therapy of cisplatin and gemcitabine apparently induced the liver and kidney damage in C57/BL mice. Bicyclol(150mg·kg-1) significantly reduced CR levels and elevated the NEUT and NEUT% in the serum dam-aged by cisplatin/gemcitabine in tumor-bearing mice. Bicycle 300mg/kg also showed the protection effect, but there was no statistical significance. RhG-CSF, the positive control, could significantly increase the WBC, NEUT and NEUT%levels reduced by cisplatin/gemcitabine. Bicyclol and rhG-CSF also slightly increased the antitumor activity of cisplatin/gemcitabine in Lewis lung tumor. Conclusion Bicyclol, especially the 150mg/kg dose, showed the potent protective activity against cisplatin/gemcitabine-induced liver and renal damage. It could decrease the mortality rate by the high-dose chemotherapy and slightly increase the associated anti-tumor effect. This may provide a new approach for preventing the hepatotoxicity and nephrotoxicity induced by cisplatin/gemcitabine in the clinic.%目的：建立顺铂（CDDP）联合吉西他滨（GEM）引起小鼠肝肾损伤动物模型，研究双环醇对CDDP/GEM联用致荷瘤小鼠肝肾损伤及骨髓毒性的保护作用。方法参考临床用药方案，建立CDDP/GEM联用致小鼠肝肾损伤模型。在模型建立的基础上，考察双环醇的保护作用：C57/BL小鼠接种Lewis肺癌后第6天开始腹腔注射CDDP（5mg·kg-1×5）及GEM（50mg·kg-1×2），建立大剂量CDDP/GEM联用致小鼠肝肾损伤模型，同时灌胃给予双环醇（150、300mg·kg-1），以吉粒芬（100 g·kg-1）作为阳性对照药。于开始给药后第6天处理动物，取瘤称重，全自动生化分析仪检测血清肝功能及肾功能生化指标，五分类血液分析仪进行血象分析。结果小鼠腹腔注射CDDP（5mg·kg-1×5）及GEM （50mg·kg-1×2），在动物尚未出现大量死亡的情况下，能引起明显的肝肾损伤。双环醇150mg·kg-1能显著降低上述方案CDDP/GEM引起的血清CR的升高，同时显著升高全血中NEUT和NEUT%。双环醇300mg·kg-1亦有保护作用，但作用不显著。吉粒芬对CDDP/GEM联用引起的WBC、NEUT、NEUT%降低有显著升高作用。双环醇及吉粒芬与CDDP/GEM合用，对后者的抑瘤活性略有增加作用。结论双环醇在略增加CDDP/GEM抑瘤活性的基础上，150mg·kg-1剂量对后者引起的荷瘤小鼠肝肾损伤及骨髓毒性具有良好的保护作用，300mg·kg-1剂量组作用不及150mg·kg-1剂量组，但均能降低荷瘤小鼠死亡率，值得临床关注。