中国药物警戒 ›› 2013, Vol. 10 ›› Issue (2): 68-70.

• 基础及临床研究 • 上一篇    下一篇

双环醇对奥沙利铂联合5-氟尿嘧啶方案引起肝损伤保护作用的实验研究

余凌虹,魏怀玲,鲍秀琦,陈晓光,张丹,孙华   

  1. 天然药物活性物质与功能国家重点实验室；中国医学科学院/ 北京协和医学院药物研究所,北京100050
  • 收稿日期:2012-09-20 修回日期:2016-03-09 出版日期:2013-02-08 发布日期:2016-03-09
  • 通讯作者: 孙华,女,博士,副研究员,硕士研究生导师,肝病药理学研究。E-mail：sunhua@imm.ac.cn
  • 作者简介:余凌虹,女,硕士,助理研究员,肝脏生化药理学。

Protection of Bicyclol on Hepatic Injury Induced by the Combination Therapy of Oxaliplatin and 5-Fluorouracil in Tumor-bearing Mice

YU Ling-hong, WEI Huai-ling, BAO Xiu-qi, CHEN Xiao-guang, ZHANG Dan, SUN Hua   

  1. State Key aboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • Received:2012-09-20 Revised:2016-03-09 Online:2013-02-08 Published:2016-03-09

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摘要： 目的 研究治疗肝炎药物双环醇在荷瘤小鼠对抗肿瘤药物奥沙利铂（oxaliplatin,L-OHP）与5-氟尿嘧啶（5-fluorouracil,5-FU）合用引起肝损伤的保护作用,并考察对抑瘤活性的影响。方法 C57/BL 小鼠接种Lewis 肺癌后6 天腹腔注射L-OHP（6mg·kg-1×1）及5-FU（25mg·kg-1×5）,建立大剂量L-OHP/5-FU 合用引起荷瘤小鼠肝损伤模型,同时给予双环醇（150,300mg·kg-1×7）。于开始给药后的第8天处理动物,取瘤称重,全自动生化分析仪分析血清ALT,AST水平,H.E.染色考察肝脏病理状态。结果 L-OHP 与5-FU合用,对Lewis 肺癌具显著抑制活性,抑瘤率达72.7%,同时出现明显毒副反应,26.7%的动物死亡,肝脏受到损伤,肝细胞出现变性、坏死,血清ALT,AST 水平升高。双环醇150、300mg·kg-1 与L-OHP/5-FU 合用,能够明显改善肝脏病理状态,降低血清转氨酶水平,减少动物死亡率,对抑瘤率亦有小的升高作用。双环醇300mg·kg-1单独给药对Lewis 肺癌的抑瘤率为25.6%,肝脏无损伤且整个实验过程中小鼠无死亡。结论 双环醇在不影响L-OHP/5-FU 抑瘤率的情况下,对后者引起的肝脏损伤有明显保护作用,能降低荷瘤小鼠死亡率,临床应用值得参考。

关键词: 双环醇, 奥沙利铂, 5-氟尿嘧啶, 肝脏损伤

Abstract: Objective To determine the effect of bicyclol against oxaliplatin/5 -fluorouracil -induced hepatotoxicity and the influence on the antitumor capacity of oxaliplatin/5 -fluorouracil in tumour -bearing mice. Methods C57/ BL mice implanted with Lewis lung tumors for6 days were treated with oxaliplatin(6mg·kg-1×1) and 5-fluorouracil (25mg·kg-1×5) to establish the liver damage model. Bicyclol(150,300mg·kg-1) was pretreated 2hr before the injection of oxaliplatin/5-fluorouracil. All animals were killed on the eighth day after oxaliplatin/5-fluorouracil treatment and tumor weight of each animal was measured. The activities of ALT and AST were meseared by automatic chemistry analyzer(TBA-40FR). Liver histopathological changes were examined by H.E. and light microscopy. Results The combination therapy of oxaliplatin and 5-fluorouracil significantly inhibited the growth of Lewis lung tumor and the inhibiton rate is 72.7% . At the same time, the obvious toxic reaction emerged expressed as 26.7% mice were death, the pathology of liver tissue was damaged and the serum aminotransferases were elevated. Bicyclol showeda significant protection as evidenced by the improvement of histotpathological injury and the decrease of elevated serum amino-transferases induced by oxaliplatin/5-fluorouracil. The administration of bicyclol could also reduce the mortality and increase slightly the anti-tumor activity of oxaliplatin/5-fluorouracil. Conclusion Bicyclol showed potent protective activity against oxaliplatin/5-fluorouracil-induced liver damage and decreased the death by the high-dose chemotherapy without affecting the associated inhibition of tumor growth. This maybe provide a new approach for preventing the hepatotoxicity induced by oxaliplatin/5-fluorouracil in the clinic.

Key words: bicyclol, oxaliplatin, 5-fluorouracil, liver damage

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