附子水提物单次给药对小鼠心脏“量-时-毒”关系研究  

Study on effect of aqueous extracts from aconite on ″dosetime-toxicity″ relationships in mice hearts

作　　者：冯群[1,2] 李晓宇[1] 栾永福[2] 孙赛男[3] 孙蓉[1] 

机构地区：[1]山东省中医药研究院,山东济南250014 [2]天津中医药大学,天津300193 [3]沈阳药科大学,辽宁沈阳110016

出　　处：《中国中药杂志》2015年第5期927-932,共6页China Journal of Chinese Materia Medica

基　　金：国家重点基础研究发展计划(973)项目(2009CB522802)

摘　　要：目的:通过心电图变化和血清生化指标的改变,研究附子水提物单次给药对正常小鼠心脏"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附子水提物,观察给药前后小鼠ECG的变化,计算心、肝、肾的脏器指数,并检测血清中肌酸激酶(CK)、乳酸脱氢酶(LDH)、B-型脑钠肽(BNP)和肌钙蛋白(CTn-I)的水平。结果:"时-毒"关系研究表明:给小鼠灌胃一定剂量附子水提物5 min后,小鼠心率开始升高,60 min达到峰值后逐渐降低;QRS间期、R波幅度、T波时间和幅度、QT间期从药后5 min开始降低,60 min达到最低值后逐渐升高;血中CK,LDH,BNP和CTn-I从药后5 min开始升高,60 min达到峰值;各时间点小鼠脏体比值无显著变化。"量-毒"关系研究表明:随着单次给药剂量的逐渐增大,小鼠的心率逐渐升高,心电图QRS间期、T波时间和幅度、QT间期逐渐减小,小鼠血清CK,LDH,BNP和CTn-I水平也逐渐升高,均呈现一定的剂量依赖性;各剂量组小鼠脏体比值无显著变化。结论:小鼠于不同剂量和不同时间点单次灌胃给予一定剂量的附子水提物可造成不同程度的心脏损伤,并呈现一定的"量-时-毒"关系,其毒性峰效应时间点出现在药后60 min。Objective： To study the effect of single administration of aqueous extracts from aconite on ＂dose-toxicity＂ relationship and ＂time-toxicity＂ relationship of mice hearts, through changes in electrocardiogram （ECG） and serum biochemical indexes. Method： Mice were grouped according to different drug doses and time points, and orally administered with water extracts from aconite for once to observe the changes of mice ECG before and after the administration, calculate visceral indexes heart, liver and kidney, and detect levels of CK, LDH, BNP and CTn-I in serum. Result： According to the ＂time-toxicity＂ relationship study, at 5 min after oral adminis- tration with aqueous extracts from aconite in mice, the heart rate of mice began rising, reached peak at 60 min and then slowly re- duced; QRS, R amplitude, T duration and amplitude and QT interval declined at 5 min, reduced to the bottom at 60 min and then gradually elevated. The levels of CK, LDH, BNP and CTn-I in serum elevated at 5 min and reached the peak at 60 min, with no sig- nificant change in ratios of organs to body at different time points. On the basis of the ＂dose-toxicity＂ relationship, with the increase in single dose of aqueous extracts from aconite, the heart rate of mice. QRS, T duration and amplitude and QT interval declined gradual- ly, and levels of CK, LDH, BNP and CTn-I in serum slowly elevated, with a certain dose dependence and no significant change in ra- tios of organs to body in mice. Conclusion： Single oral administration of different doses of aqueous extracts from aconite could causedifferent degrees of heart injury at different time points, with a certain dose dependence. Its peak time of toxicity is at 60 min after the administration of aqueous extracts from aconite.

关 键 词：附子 心脏毒性 “量-时-毒”关系 

分 类 号：R285.5[医药卫生—中药学]