何首乌不同组分单次给药对小鼠肝毒性“量-时-毒”关系研究

目的观察何首乌不同组分单次给药对小鼠肝毒性"量-时-毒"关系的影响。方法 "时-毒"关系研究:取小鼠按不同时间点分组,单次灌胃给予一定剂量的何首乌水提组分、醇提组分,观察给药后小鼠死亡情况和毒性反应,分别于药后不同时间检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST),计算肝、脾、胸腺脏器指数。"量-毒"关系研究:取小鼠按不同剂量分组,单次灌胃给予不同剂量的何首乌水提组分、醇提组分,分别于药后4h、2h按"时-毒"研究方法对小鼠进行相应处理。结果小鼠灌胃较高剂量何首乌水提组分后,血清ALT、AST活力在4h达到高峰,持续时间均约达24h;给药4h后小鼠出现肝脏明显肿大,肝指数升高,其中4～6h肝脏指数升高较为明显。小鼠灌胃较高剂量何首乌醇提组分后,血清ALT、AST活力在2h达到高峰,持续时间均约达48 h;给药2 h后小鼠出现肝脏明显肿大,肝指数升高,其中2～4h肝脏指数升高较为明显。何首乌水提组分剂量在(5.5～30.75)g.kg-1之间、醇提组分在(8.5～24.5)g.kg-1之间对肝组织产生明显损伤,且随着剂量增大,ALT、AST升高显著。结论小鼠单次灌胃给予一定剂量的何首乌水提组分或醇提组分可造成急性肝损伤,并呈现一定的"量-时-毒"关系。关于其肝脏损伤的机制有待进一步研究。

Experimental Study on the "Dose-Time-Toxicity "Relationship of Acute Hepatotoxicity Induced by Different Components from Polygonum multiflorum in Mice

Objective To study the ＂dose-time-toxicity＂ relationship of hepatotoxicity caused by single dose water extracted and alcohol extracted components of Polygonum multiflorum to mice.Methods Mice are grouped according to different time or dose points,to observe the death condition and toxicity of mice,detect ALT、AST in serum,calculate liver,spleen,thymus index.Results Compared with the control group,ALT,AST level in serum of water extracted components are peaked after 4 hours＇ administration,and restored near normality after 24 hours;ALT,AST level in serum of alcohol extracted components are peaked after 2 hours＇ administration,and restored near normality after 48 hours;The water extracted components of（5.5~30.75）g·kg-1 and alcohol extracted components of（8.5~24.5）g·kg-1 have obvious damage to the liver organization,and ALT,AST in serum increased significantly with the dose increasing.Conclusion The water extracted and alcohol extracted components gavaged certain dose one time to mice could cause obvious acute hepa-injury,and there were certain time-toxicity and dose-toxicity relationships.