右归饮的毒性研究

Toxicity Study of the Herbal Formula Youguiyin

目的:评价右归饮口服给药的安全性,为临床安全用药提供合理的科学依据。方法:1.以右归饮最大药液浓度和小鼠最大灌胃体积,24 h内3次给予小鼠,检测一般体征、血常规、血生化指标以观察14 d内动物的急性毒性反应。2.大鼠灌胃给予60 g/kg右归饮,每天1次,连续90 d,停药后观察30 d,观察大鼠活动、形态、每周体重变化和死亡情况,检测其血常规、血生化和主要脏器大体形态、脏器指数、病理形态。结果:右归饮给药后小鼠在14 d的观察期内未出现死亡和异常情况;与空白组对比,右归饮组体重、卵巢、子宫、胸腺、脾、心、肾、胃、脑等主要脏器指数无显著性差异;血常规和血生化指标均无显著改变。右归饮给药后大鼠在给药期及恢复期内未见死亡;与空白组相比,右归饮组大鼠在各个时间点的外观形态均无显著差异,大鼠体重、脑、胸腺、心、肝、肾、肾上腺、子宫、卵巢、睾丸、附睾等主要脏器的外观形态和脏器系数均无显著差异。给药90 d及停药30 d后,与空白组相比,右归饮组血清中ALT、AST、ALP、ALB、TP、TG、GLU、T-CHO和CREA均无显著差异。给药90 d后,血清中UREA明显降低,CK明显增高;停药30 d后,血清中ALT、AST、ALP、TP、GLU、T-CHO、UREA和CK有显著差异,但都在正常大鼠的生理范围内,血常规各指标无明显变化,脑、胸腺、心、肝、肾、肾上腺、子宫、卵巢、睾丸、附睾等主要脏器的脏器系数及病理学检查均无显著变化。结论:右归饮24小时内3次灌胃给药共计720 g/kg,相当于人临床拟用药量(81 g/kg)的533倍,未见小鼠显著毒性反应;60 g/kg连续灌胃给药90 d,相当于人临床拟用药量(81 g/kg)的44倍,未见大鼠显著毒性反应。提示右归饮口服用药安全性较高。

To evaluate the toxicity of Youguiyin in the oral medication,to provide scientific basis for clinical safety.Methods:1 Youguiyin was given to mice in maximum concentration and maximum gastric volume,3 times in 24 h.The general physical signs,blood routines and blood biochemical indicators were observed to study the acute toxicity within 14 days.2 The rats were intragastrically administered with 60 g/kg Youguiyin for 90 days,once a day,and the recovery period was 30 days.The activities,appearances,body weights and death of the rats were observed.The blood routines,blood biochemical indicators,organ general morphology,organ index and pathological changes were determined.Results:In 14 days of toxicity test,no death or abnormal changes was observed.Compared with the control group,the body weight,blood routine,blood biochemistry,and organ indexes(ovary,uterus,thymus,spleen,heart,kidney,lung and brain)showed no significant difference.In 90 days of toxicity test and 30 days of recovery,there was no death and abnormal conditions.Compared with the control group,the physical changes,body weight and organ indexes(ovary,uterus,thymus,spleen,heart,kidney,lung and brain)showed no significant difference.No significant difference was discovered in serum levels of ALT、AST、ALP、ALB、TP、TG、GLU、T-CHO and CREA.After 90 days of administration,serum levels of UREA and CK were significantly increased.In the 30 days of recovery,serum levels of ALT,AST,ALP,TP,GLU,T-CHO,CREA and CK were changed,within physiological ranges.No significant differences were observed in blood routine,blood biochemistry,pathological changes and organ indexes(ovary,uterus,thymus,spleen,heart,kidney,lung and brain).Conclusion:Youguiyin administered for 3 times in 24 hours,720 g/kg totally(equal to 533 times of clinical dosage at 81 g/kg),has no toxicity reaction in mice.Youguiyin administered for 90 days at the dose of 60 g/kg(equal to 44 times of clinical dosage at 81 g/kg),has no toxicity reaction on rats.The results suggest Youguiyin is safe in the oral medication.,Youguiyin is safe and no potential toxicity,has a good prospect on clinic.