附子水提组分多次给药对小鼠心脏毒性“量-时-毒”关系研究

摘要

目的通过心电图变化和血液指标改变研究附子水提组分多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，多次灌胃给予一定剂量的附子水提组分，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）的含量。结果“时-毒”关系研究表明：给小鼠灌胃附子水提组分24 h后，小鼠心率降低，P波时间延长、幅度变大，P-R间期、QRS波群时程变长；QT间期缩短；心脏指数降低，血中CK、LDH含量升高。药后48 h上述变化更加显著。“量-毒”关系研究表明：小鼠药后心率升高，P波时间延长、幅度增大；P-R间期延长；QRS波群和QT间期延长，QT间期长短与心率的快慢成反比关系；心脏指数降低，血中CK、LDH含量升高，而肝脏、肾脏指数的改变则不显著。且上述变化具有一定的剂量依赖性。结论小鼠于不同剂量和不同时间多次灌胃给予一定剂量的附子水提组分可造成不同程度的心脏损伤，并呈现一定的“量-时-毒”关系。关于其心脏损伤的机制有待进一步研究。%Objective To study the influences of"dose-toxicity"relationship and"time-toxicity"relationship of cardiotoxicity, through electrocardiogram (ECG) and serum biochemical indexes changes caused by multiple doses Aconite water extract on mice. Methods Mice were grouped according to different time or dose points, and given multiple doses of Aconite water extract by gavage respectively. Changes of ECG were observed. The ratio of heart, liver and kidney to body was measured, the contents of CK and LDH related to cardiotoxicity in serum were detected. Results The"time- toxicity" relationship showed that the heart rate of mice dropped 24 hours later of administration compared with normal group. The duration of P extended and the amplitude enlarged. P-R interval, QRS extended and QT interval reduced. Cardiac index decreased while the contents of CK and LDH increased. All changes of them were more statistically significant 48 hours later. The "dose- toxicity" relationship showed that the heart rate of mice and the contents of CK and LDH in serum elevated. P-R interval, QRS and QT interval extended and the length of QT interval was inversely proportional to heart rate. Cardiac index decreased and there was no significant change of liver index and kidney index among different groups. All changes of them showed a dose dependent manner. Conclusion Aconite water extract which is gavaged with a single dose to mice can cause cardiotoxicity and there is a certain relationship of"dose-time-toxicity". However the mechanism of cardiotoxicity will obviously require further investigation.