中国药物警戒 ›› 2012, Vol. 9 ›› Issue (11): 652-654.

• 基础及临床研究 • 上一篇    下一篇

柴胡总皂苷肝毒性肝纤维化损伤机制研究

张丽华1, 吕莉莉2, 张亚囡3, 黄伟2, 孙蓉2*   

  1. 1 山东大学附属济南市中心医院,山东 济南 250013；
    2 山东省中医药研究院,山东 济南 250014；
    3 山东中医药大学,山东 济南 250355
  • 收稿日期:2012-07-22 出版日期:2012-11-10 发布日期:2015-08-07
  • 通讯作者: 孙蓉,研究员,博士生导师,中药药理与毒理。E-mail： sunrong107@163.com
  • 作者简介:张丽华,女,学士,副主任医师,神经内科与药物治疗。
  • 基金资助:
    国家自然科学基金项目（30672649）,（81073148）; 山东省科技平台建设项目（2008GG2NS02021）; 山东省国际合作引智项目（L20083700336）; 国家重点基础研究发展计划 （973）中医基础理论专项资助项目（2009CB522802）

Study on the Hepatotoxicity Mechanism of Bupleurum Saikosaponin by Alcohol Elution on Hepatic Fibrosis

ZHANG Li-hua1, LV Li-li2, ZHANG Ya-nan3, HUANG Wei2, SUN Rong2*   

  1. 1 Jinan Central Hospital Affiliated to Shandong University, Shandong Jinan 250013, China;
    2 Shandong Research Academy of TCM, Shandong Jinan 250014, China;
    3 Shandong University of Traditional Chinese Medicine, Shandong Jinan 250355, China
  • Received:2012-07-22 Online:2012-11-10 Published:2015-08-07

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摘要： 目的探讨柴胡总皂苷肝毒性损伤与肝脏纤维化的相关性,为阐明其肝毒性机制提供依据。方法大鼠连续15天灌胃高、中、低不同剂量,按等生药量计算,高、中、低剂量分别为300、150、50 mg ·kg-1,末次药后取血和肝组织,检测血清及肝组织匀浆中羟脯氨酸含量的变化;并作大鼠肝脏组织Masson's病理学检查。结果15天给药结束后药物组大鼠血清和肝组织羟脯氨酸含量均明显升高,随给药剂量增加羟脯氨酸含量升高幅度增大,与正常对照组比较呈现不同程度的显著性差异;马松染色肝组织病理改变可见胶原纤维延伸明显,并互相连接包绕整个肝小叶,导致正常肝小叶结构破坏,假小叶形成。药物高、中、低剂量之间的肝毒性损伤程度有一定的剂量依赖关系,与空白组相比有明显差异。结论连续15天灌服一定剂量的柴胡总皂苷可导致大鼠明显的肝纤维化,柴胡总皂苷是其肝毒性主要物质基础,为柴胡总皂苷的肝毒性评价提供了实验依据,为其毒性预警和临床安全应用提供对策及科学依据。

关键词: 柴胡总皂苷, 肝毒性, 肝纤维化, 羟脯氨酸

Abstract: ObjectiveTo study the hepatotoxity mechanism of refined products from Bupleurum Saikosaponin by Alcohol Elution, and to discuss the relevance between hepatotoxcity and hepatic fibrosis, in order to provide the basis of hepatotoxity mechanism. MethodsRefined products from Bupleurum Saikosaponin by alcohol elution of different dosages(ig) were given to Wistar rats for fifteen days consecutively. The changes of hydroxyproline in serum and liver tissue were detected and the histopathological study was performed. ResultsOn the 15th day after ig the level of hydroxyproline in serum and liver tissue increased obviously, which is in line with the dosages increased. Masson staining shows the pathological changes of liver collagen fiber extension is obvious, and connected to each other surrounding the hepatic lobule, leading to destruction of the normal lobular architecture, false lobule. Compared with the control group, the degree of liver damage has certain dependence on the dose. ConclusionLong-term administration of the refined products from Bupleurum Saikosaponin by alcohol elution with large doses can result in liver fibrosis in rats; the results of this study provide some experimental basis for the safe use of Bupleurum inclinical .The total Bupleurum saikosaponin was the main material basis of hepatoxicity.

Key words: Bupleurum Saikosaponin, hepatotoxicity, hepaticfibrosis, hydroxyproline