摘要
目的:研究单次给予柴胡总皂苷致小鼠肝毒性损伤的机制及其时毒、量毒关系。方法:按小鼠急性肝毒性"量-时-毒"关系研究方法进行,"时-毒"关系研究:小鼠灌胃一定剂量(36.075 g/kg)的柴胡总皂苷提取物,分别于给药后不同时间点检测血清谷胱甘肽S转移酶(GST)、乳酸脱氢酶(LDH)水平;"量-毒"关系研究:给小鼠灌胃不同剂量(36.075、21.650、12.975、7.925、4.675 g/kg)的柴胡总皂苷提取物,于给药后2 h检测血清谷胱甘肽S转移酶(GST)、乳酸脱氢酶(LDH)水平。结果:对柴胡总皂苷致小鼠肝毒性"时-毒"关系研究显示:小鼠单次灌胃柴胡总皂苷提取物后1 h血清GST、LDH水平开始升高,与0 h组比较有极显著性差异;血清GST、LDH水平均于药后12 h达到峰值,之后逐渐恢复。对柴胡总皂苷致小鼠肝毒性"量-毒"关系研究显示:小鼠单次灌胃不同剂量的柴胡总皂苷提取物后2h血清GST、LDH水平均有不同程度升高,且呈现一定的剂量相关性。结论:小鼠单次灌服一定剂量柴胡总皂苷提取物可造成急性肝损伤,并呈现一定的时毒、量毒关系;影响肝脏能量代谢是柴胡总皂苷致小鼠肝毒性损伤的途径之一。
Objective: To observe the mechanism and dose-time-toxicity relationship of the hepatotoxicity damage on mice after being administrated the extracts of total saikosaponihs once. Methods: Study on the "time-toxicity" relationship: mice were administrated with certain dosage which was 36. 075g/kg of the extracts of total saikosaponins and the changes of the active units of GST and LDH were tested at different time points after administration, Study on the "dosage-toxicity" relationship: mice were administrated with different dosages which were 36. 075, 21. 650,12. 975,7. 925,4. 675 g/kg respectively of the extracts of total saikosaponins and the corresponding treatment was performed at 2h af- ter administration in accordance with the method of "time-toxicity" relationship study. Results: The "time-toxicity" relationship study indi- cated that the level of GST and LDH in serum began to increase at lh after administration, and have obvious differences compared with the control group, then they both reached the peak level at 12h. The "dose-toxicity" relationship study indicated that compared with the control group, the level of GST and LDH in serum increased to different degree at 2h after administration, which showed an correlation with the dos- age. Conclusion: Once oral administration of saikosaponins extracts from Bupleurum Chinense with certain dosage may induce acute hepato- toxical injury in mice and show an obvious "dosage-time-toxicity" relationship. One of the mechanisms that mice are hepatotoxicity- induced by SS is to influence the energy metabolism of liver.
出处
《中药药理与临床》
CAS
CSCD
北大核心
2012年第4期60-62,共3页
Pharmacology and Clinics of Chinese Materia Medica
基金
国家自然科学基金项目(81073148、30672649)
国家973计划中医基础理论专项课题(2009CB522802)
山东省科技平台建设项目课题(2008GG2NS02021)
关键词
柴胡总皂苷
能量代谢
小鼠
肝毒性
早期靶标
saikosaponins
energy metabolism
mice
hepatotoxicity
early targets