决明子不同提取物单次给药对小鼠肝、肾“量-时-毒”关系研究

摘要

目的 通过血清生化指标改变的表现,研究决明子不同提取物单次给药对正常小鼠肝脏、肾脏“量-毒”和“时-毒”关系的影响.方法 根据给药剂量和药后不同时间点对小鼠分组,单次灌胃给予一定剂量的决明子全粉、水提物和醇提物,计算肝、肾的脏器指数,并检测血清中谷丙转氨酶(ALT)、谷革转氨酶(AST)、肌酐(Cr)、尿素氮(BUN)、肿瘤坏死因子-α(TNF-α)的水平.结果 “时-毒”关系研究表明:给予小鼠决明子不同提取物后,小鼠血清各项指标(ALT、AST、Cr、BUN、TNF-α)均在给药后1～2 h达到高峰,48h开始恢复.“量-毒”关系研究表明:小鼠单次灌胃决明子醇提物(79.80 ～26.84)g·kg-1、决明子水提物(57.45 ～23.53)g ·kg-1、决明子全粉15.00 g ·kg-1可造成明显肝、肾毒性损伤,血清ALT、AST、BUN、Cr、TNF-α水平明显升高,上述剂量范围分别相当于临床70 kg人日用量的(387.4～130.3)倍、(294.0～120.5)倍、140.0倍.结论 单次给予正常小鼠不同剂量和不同时间的决明子水提物、决明子醇提物可造成不同程度的肝、肾损伤,并呈现“量-时-毒”关系,决明子全粉各剂量组无剂量依赖关系,可能与药品的浓度较高,影响肠道吸收有关.%Objective To reach the influences of different extracts from Cassiae Semen on "dose-toxicity" relationship and "time-toxicity" relationship of hepatotoxicity and nephrotoxicity in mice by serum biochemical indexes and pathological.Methods Mice were grouped according to different time or dose points,and given all-components,water extracted components and alcohol extracted components by gavage respectively.The ratio of liver and kidney to body was measured,the contents of ALT、AST、Cr、BUN and TNF-α related to hepammxicity and nephrotoxicity in serum were detected.Results The "time-toxicity" relationship showed that after the mice were given different extracts of Cassiae Semen,the serum indexes (ALT,AST,Cr,BUN and TNF-α) in mice reached the peak at 1～2 h after treatment,and 48 h began to recover.The "dose-toxicity" relationship showed that:after single intragastric administration of alcohol extracted components(79.80～26.84)g· kg-1,water extracted components(57.45 ～23.53)g·kg-1,all-components 15.00 g ·kg-1 can cause obvious damage in liver and kidney,the serum ALT,AST,BUN,Cr,TNF-levels were significantly increased,which was respectively equal to (387.4～130.3) times,(294.0～120.5) times and 140.0 times of the clinical daily dosage in 70 kg humans.Conclusion Alcohol extracted components and water extracted components which were gavaged with different dose to mice can cause hepatotoxicity and nephrotoxicity and there was a certain relationship of "dose-rime-toxicity".However the all-components was no dose-dependent relationship,may be related to the higher concentration of drugs,affecting intestinal absorption.