双环醇对雷公藤多苷诱导小鼠肝损伤的保护作用研究

中国药物警戒 ›› 2016, Vol. 13 ›› Issue (7): 385-388.

• 基础与临床研究 • 下一篇

双环醇对雷公藤多苷诱导小鼠肝损伤的保护作用研究

刘宁, 张友文, 张丹, 鲍秀琦, 孙华

中国医学科学院/北京协和医学院药物研究所，天然药物活性物质与功能国家重点实验室，北京100050

收稿日期:2016-06-21 修回日期:2018-07-17 出版日期:2016-07-20 发布日期:2018-07-17
通讯作者: 孙华，博士，副研究员·硕导，肝脏生化药理学。E-mail：sunhua@imm.ac.cn
作者简介:刘宁，女，在读硕士，肝脏生化药理学。
基金资助:
国家科技计划863项目（2014AA021101）；国家自然科学基金项目（81173073）。

Protective Effect of Bicyclol on Glucosides of Tripterygium Wilfordii-induced Liver Injury in Mice

LIU Ning, ZHANG You-wen, ZHANG Dan, BAO Xiu-qi, SUN Hua

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

Received:2016-06-21 Revised:2018-07-17 Online:2016-07-20 Published:2018-07-17

摘要/Abstract

摘要： 目的考察双环醇对雷公藤多苷致小鼠药物性肝损伤模型的保护作用及初步机制。方法 ICR小鼠灌胃给予双环醇（50、100、200 mg·kg^-1×3），于末次给药后2 h单次灌胃给予雷公藤多苷300 mg·kg^-1，观察动物状态，禁食18 h后处理动物，制备血清，全自动生化分析仪检测血清ALT、AST及LDH水平，H.E.染色考察肝脏病理状态，Western blot法分析蛋白表达。结果雷公藤多苷300 mg·kg^-1 能引起小鼠显著毒性和肝脏损伤，动物死亡率达41.67%，血清肝功能生化指标ALT、AST及LDH含量均显著升高，肝组织出现以炎症细胞浸润、肝细胞坏死为主要特征的病理改变。50、100、200 mg·kg^-1双环醇对雷公藤多苷引起的小鼠肝毒性有显著保护作用，能降低小鼠死亡率，降低雷公藤多苷引起的小鼠血清ALT、AST及LDH的升高，改善肝组织病理状态。初步机制研究显示，双环醇可降低凋亡相关蛋白Fas L的表达，上调PI3K和connexin-43的表达。结论双环醇对雷公藤多苷所致药物性肝损伤具有显著的保护作用，该保护作用可能与其抑制肝细胞凋亡，改善肝组织细胞间缝隙连接有关。

关键词: 雷公藤多苷, 双环醇, 药物性肝损伤, 胞间缝隙连接通讯

Abstract: Objective To study the protective effect of bicyclol on glucosides of Tripterygium wilfordii-induced liver injury in ICR mice. Methods ICR mice were given intragastric administration bicyclol (50, 100, 200 mg·kg^-1) for three times. Two hours after the last administration, the mice were treated with glucosides of Tripterygium wilfordii 300 mg·kg^-1 to establish the liver damage model. All animals were killed on 18 h after glucosides of Tripterygium wilfordii treatment. The activities of ALT, AST and LDH in serum were measured by automatic chemistry analyzer. Liver histopathological changes were examined by H.E. and light microscopy. Western blot was carried out to analyze the protein level of liver. Results Glucosides of Tripterygium wilfordii 300 mg·kg^-1 could induce significant toxicity and liver damage, the mortality rate of mice was 41.67%. The levels of serum ALT, AST, LDH significantly increased and there were hepatocyte apoptosis and inflammatory cell infiltration in liver tissue. 50, 100, 200 mg·kg^-1 bicyclol could reduce the mortality rate of mice and the blood biochemical indexes, including ALT, AST and LDH. The results of H.E. staining showed that bicyclol could prevent the steatosis of liver and colliquative necrosis of liver cells. The results of Western blot showed that bicyclol could simulate PI3K pathway, decrease the expression of Fas L, and increase the expression of connexin-43. Conclusion Bicyclol showed a significant protective effect on glucosides of Tripterygium wilfordii -induced liver injury in mice. This may be in connection with inhibiting apoptosis and recovering the gap junctions intercellular communication.

Key words: glucosides of Tripterygium wilfordii, bicyclol, DILI, gap junction

中图分类号:

R965

刘宁, 张友文, 张丹, 鲍秀琦, 孙华. 双环醇对雷公藤多苷诱导小鼠肝损伤的保护作用研究[J]. 中国药物警戒, 2016, 13(7): 385-388.

LIU Ning, ZHANG You-wen, ZHANG Dan, BAO Xiu-qi, SUN Hua. Protective Effect of Bicyclol on Glucosides of Tripterygium Wilfordii-induced Liver Injury in Mice[J]. Chinese Journal of Pharmacovigilance, 2016, 13(7): 385-388.

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双环醇对雷公藤多苷诱导小鼠肝损伤的保护作用研究

Protective Effect of Bicyclol on Glucosides of Tripterygium Wilfordii-induced Liver Injury in Mice

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