中国药物警戒 ›› 2014, Vol. 11 ›› Issue (4): 198-202.

• 基础研究 • 上一篇    下一篇

水溶性联苯类化合物WLP-S-14在实验性肝损伤模型中的保护作用

苗露阳1, 2, 童元峰1, 吴松1, 魏怀玲1, 鲍秀琦1, 张丹1, 张予阳2, 孙华1*   

  1. 1中国医学科学院/北京协和医学院药物研究所,北京100050;
    2沈阳药科大学,辽宁 沈阳110016
  • 收稿日期:2013-04-17 修回日期:2016-02-03 出版日期:2014-04-08 发布日期:2016-02-03

Protective Effect of Water Soluble Biphenyl Compound WLP-S-14 on Experimental Liver Injury Model

MIAO Lu-yang1, 2, TONG Yuan-feng1, WU Song1, WEI Huai-ling1, BAO Xiu-qi1, ZHANG Dan1, ZHANG Yu-yang2, SUN Hua1, *   

  1. 1Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;
    2Shenyang Pharmaceutical University, Liaoning Shenyang 110016, China
  • Received:2013-04-17 Revised:2016-02-03 Online:2014-04-08 Published:2016-02-03

PDF (PC)

179

摘要： 目的考察新型水溶性联苯类化合物WLP-S-14在3种实验性小鼠肝损伤模型中的保护作用。方法建立四氯化碳（CCl4）、刀豆蛋白A（Con A）诱发的小鼠急性肝损伤模型,WLP-S-14（100、200 mg·kg-1）在给予肝毒性物质前2天连续3次腹腔注射给药,全自动生化分析仪检测血清ALT及AST水平。建立奥沙利铂（Oxaliplatin,L-OHP）联合5-氟尿嘧啶（5-Fluorouracil,5-FU）诱发的荷瘤小鼠肝损伤模型,WLP-S-14（100、200 mg·kg-1）腹腔注射给药,连续7天,H.E.染色观察肝脏病理状态,全自动生化分析仪检测血清ALT及AST水平,同时计算抑瘤率并观察动物死亡情况。结果在CCl4诱导的急性中毒性肝损伤模型,WLP-S-14 100 mg·kg-1对CCl4引起的小鼠血清ALT、AST的升高均有显著降低作用,WLP-S-14 200mg·kg-1对ALT的降低作用显著,对AST仅有降低的趋势但无统计学意义;在Con A诱导的急性免疫性肝损伤模型中,WLP-S-14 100、200mg·kg-1可显著降低Con A引起的血清ALT、AST升高,200mg·kg-1活性略优于同剂量的双环醇组;在L-OHP联合5-FU诱发的荷瘤小鼠药物性肝损伤模型,WLP-S-14 100、200mg·kg-1对L-OHP/5-FU引起的荷Lewis肺癌小鼠肝脏损伤表现显著改善作用,能降低血清ALT、AST水平,改善肝脏病理状态。WLP-S-14 100 mg·kg-1对L-OHP/5-FU的抑瘤率无降低作用,且能改善小鼠因L-OHP/5-FU而引起的体重下降状况。结论新型水溶性联苯类化合物WLP-S-14对多种原因引起的小鼠肝损伤均显示显著的保护作用,值得进一步开发研究。

关键词: 联苯类化合物, 双环醇, 水溶性, 肝损伤中图分类号：R978.11, R969.3

Abstract: ObjectiveTo assess the hepatoprotective effect of a water solubility derivative of biphenyl by three acute liver failure models. MethodsTwo mice models of acute liver failure were established by injection with carbon tetrachlo-ride(CCl4) or concanavalin A(Con A) respectively. Mice were intraperitoneally injected with two doses of WLP-S-14(100 200 mg·kg-1) before administration of CCl4 and Con A. Serum alanine aminotransferase(ALT) and glutamate oxaloacetate transaminase(AST) were detected by automatic chemistry analyzer(TBA-40FR). At the same time, oxaliplatin and 5-fluorouracil were injected to induce liver failure in Lewis-bearing mice. WLP-S-14(100,200mg·kg-1) was pretreated 2hr before the injection of oxaliplatin/5-fluorouracil. The activities of ALT and AST in serum were measured by automatic chemistry analyzer and liver histopathological changes were examined by H.E. and light microscopy. ResultsIn CCl4-induced liver damage mice, WLP-S-14 100mg·kg-1 significantly reduced the elevated serum AST and ALT levels induced by CCl4. WLP-S-14 200mg·kg-1 also markedly decreased sersum ALT, but there was no significantly statistical significance on the decrease of AST when compared with the model group. In Con A-induced immunologic liver injury mice, pretreation of WLP-S-14(100 200mg·kg-1) both markedly decreased the elevated ALT and AST induced by Con A. WLP-S-14(100, 200mg·kg-1) also showed a significant protection in oxaliplatin/5-fluorouracil-induced liver damage mice, as evidenced by the improvement of histopathological injury and the decrease of elevated serum aminotransferases. There was no decline to tumor inhibition rate produced by oxaliplatin/5-fluorouracilwhenco-administration WLP-S-14 100mg·kg-1. ConclusionWLP-S-14 showed potent protective activities against CCl4, Con A or oxaliplatin/5-fluorouracil-induced liver damage. It is worth exploring for future study.

Key words: derivative of biphenyl, bicyclol, water solubility, liver injury

中图分类号: