摘要
目的:研究熟大黄对大鼠肝脏的量-效/毒关系,探讨熟大黄保肝与损肝的"双向"作用及炮制减毒的客观真实性。方法:同时采用正常和病理动物,在较大剂量范围(生药2.0,5.4,14.7,40.0 g·kg-1·d-1)考察熟大黄总提物对实验动物一般状态、生化指标和组织病理的影响,并通过因子分析方法综合分析熟大黄量-效/毒关系。结果:采用因子分析法从给药后显著变化的9个生化指标中抽提出2个公因子,公因子1主要由HA,LN和TGF-β1主导,可解释为纤维化因子;公因子2主要由ALT,AST和ALP主导,可解释为细胞损伤因子。因子分析结果表明熟大黄对大鼠肝脏存在明显的药效与毒性"双向"作用:对CCl4诱导的慢性肝损伤具有显著的保护作用,而对正常动物具有一定的肝毒性作用。病理检查结果与因子分析结果一致。可比剂量下,熟大黄的保肝作用强于生大黄,而毒性较低。结论:熟大黄对正常动物具有一定的肝毒性作用,但用于肝损伤动物具有显著的治疗作用,在一定程度上印证了"有故无殒"之说和辨证用药减毒的科学性。"有故无殒"思想对正确认识与研究中药量-效/毒关系、指导辨证用药具有重要价值。
Objective：To investigate the dosage-efficacy/toxicity relationship of prepared rhubarb,in order to explore the bidirectional effects in hepatoprotection and hepatotoxicity of prepared rhubarb and the objective authenticity for attenuating toxicity by processing.Method：Normal and pathological animals were adopted simultaneous to investigate the effect of total extracts from prepared rhubarb within a high dose range（2.0,5.4,14.7,40.0 g·kg- 1·d- 1） on normal state,biochemical index and histopathology of experimental animals.The factor analytic approach was used to analyze the dosage-efficacy /toxicity relationship of prepared rhubarb.Result：The factor analytic approach was used to extract two common factors from the nine biochemical indexes.The firs common factor was mainly dominated by HA,LN and TGF-β1,and could be explained as fibrotic factors.The second common factor was mainly dominated by ALT,AST and ALP,and could be explained as cellular factor.The results of the factor analysis suggested that prepared rhubarb showed significant bidirectional effects in hepatoprotection and hepatotoxicity,which could protect liver in CCl4 injured chronic hepatic injury,but had a certain hepatotoxic effect to normal animals.The pathological examination showed consistent results with the factor analysis.Under comparable dosages,prepared rhubarb showed a stronger liver protecting effect than crude rhubarb,with a lower toxicity.Conclusion：Although prepared rhubarb has a certain hepatotoxic effect to normal animals,it has also a significant therapeutic effect to animals with liver injury.The results proved the symptom-based prescription theory and the scientificity of the symptom-based medication.The symptom-based prescription theory is important to correctly realize the dosage-efficacy /toxicity relationship of traditional Chinese medicines and guide the symptom-based medication.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2014年第15期2918-2923,共6页
China Journal of Chinese Materia Medica
基金
国家自然科学基金项目(81373984
81173571)
中央本级课题(20603020101)
关键词
熟大黄
量-效/毒关系
保肝
肝损伤
因子分析
炮制减毒增效
prepared rhubarb
dosage-efficacy/toxicity relationship
liver protection
hepatotoxicity
factor analysis
toxicityattenuating and efficacy-enhancing by processing
