基于证候理论观察白附片对正常和肾阳虚证大鼠心肌酶的影响

Influence of White Prepared Lateral Root of Aconite on Cardiac Enzymes in Normal and Kidney-Yang Insufficiency Rats

目的:观察白附片对正常大鼠和肾阳虚证大鼠心肌酶的影响,探索其对两种大鼠心脏毒性的差异。方法:80只SD雄性大鼠随机平均分为肾阳虚模型组和正常组;肾阳虚模型组采用肌注氢化可的松琥珀酸钠的方法造模;造模结束后,把两组大鼠各自随机分为低剂量、小剂量、中剂量和大剂量给药组和空白对照组,每组8只;对各给药组大鼠连续14 dig不同浓度的白附片溶液;末次给药24 h后处死动物,制备血清和心肌组织匀浆;检测血液肌酸激酶(CK)和乳酸脱氢酶(LDH),放射性免疫法检测促肾上腺皮质激素(ACTH)、皮质醇(COR)、环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP),免疫比浊法检测心肌琥珀酸脱氢酶(SDH)和钠-钾三磷酸腺苷酶(Na+-K+-ATPase)。结果:与正常大鼠比较,模型大鼠血液中ACTH、COR、cAMP水平降低而cGMP升高;白附片可引起正常大鼠CK的升高和Na+-K+-ATPase的下降,而对模型大鼠没有影响;随着白附片剂量的增加,正常和模型大鼠的LDH有升高的趋势,而SDH有下降的趋势,而且正常大鼠变化的幅度更大。结论:白附片对正常大鼠的心脏毒性比对肾阳虚模型大鼠更突出;该研究为在证候理论指导下进行中药毒性评价的合理性和必要性提供了客观依据。

Objective：To observe influence of White Prepared Lateral Root of Aconite on cardiac enzymes in normal and Kidney-Yang insufficiency rats and explore the difference of both. Method：Eighty Sprague-Dawley（SD）male rats were divided randomly into normal group and Kidney-Yang insufficiency model group, forty rats in each group. After producing Kidney-Yang insufficiency model by injecting hydrocortisoni natrii succinas in intramuscular, normal and model rats were respectively and randomly divided into little, low, medium, great dose group and blank group, eight rats in each group. Those rats were administered orally with different concentrations of white prepared lateral root of aconite every day for two weeks. After twenty-four hour the last oral administration, blood serum and cardiac muscle tissue homogenate were prepared and used for testing creatine kinase （CK）, lactate dehydrogenase （LDH）, cardiac muscle succinate dehydrogenase（SDH）,Na^＋ -K^＋ -ATPase, adrenocorticotrophic hormone（ACTH）, hydrocortisone （COR）, cyclic adenosine monophosphate（cAMP）and cyclic guanosine monophosphate（cGMP）. Results： Hydrogenation cortisone caused cAMP and COR descend, but cGMP increase. With adding dose, all rats LDH squinted towards going up, normal rats＇ LDH going up was quicker than model rats＇, which indicated mainly abnormal influence on surrounding cardiac muscle enzyme. However, all rats SDH and Na^＋ -K^＋ -ATPase had a trend of descending. Normal rats＇ SDH descending was quicker than model rats＇, which showed white prepared lateral root of aconite also impacted rats＇cardiac muscle mitoehondrion enzyme. Conclusion： White prepared lateral root of aconite had less cardiac toxicity on Kidney-Yang insufficiency rats. This study provided objective evidence for the theory of evaluating traditional Chinese herbal toxicity based on animal model with a specific TCM syndrome.