目的 考察黄草乌炮制前后两种生物碱含量变化及其对心脏的毒性影响。方法 采用UPLC法测定黄草乌炮制前后滇乌碱、8-去乙酰滇乌碱的含量；采用Bliss法测定黄草乌生品的大鼠半数致死量（LD₅₀）；连续ig给药14 d，观察麻醉大鼠Ⅱ导联心电图变化，检测血清中肌酸激酶（CK）和乳酸脱氢酶（LDH）的水平，观察心肌病理组织形态学变化等。结果 黄草乌炮制前后滇乌碱的含量分别为263.96 μg/g、未检出，8-去乙酰滇乌碱的含量分别为未检出、568.47 μg/g；生品LD₅₀为生药4.2 g/kg，炮制品最大给药量为生药18.0 g/kg；连续ig给药14 d，生品组麻醉大鼠先后出现室性早搏、室性二联律和室颤等，炮制品组前期出现心动过缓，60 min恢复正常；与对照组比较，生品组血清LDH和CK水平均显著升高（P<0.05），炮制品组只有LDH水平显著升高（P<0.05）；生品组心肌纤维之间间隙明显扩大，炎细胞浸润明显；炮制品组心肌纤维排列较整齐，间质中可见个别炎细胞浸润。结论 在所给的剂量下，黄草乌生品对心脏毒性较强，炮制后毒性明显降低。

Objective To investigate the content changes of two alkaloid before and after the processing of Aconitum vilmorinianum and its effect on cardiotoxicity. Methods The UPLC method was used to determine the content of yunaconitine and 8-acetylacetonarine before and after the processing of A. vilmorinianum. The half lethal dose (LD₅₀) of A. vilmorinianum to rats was determined by Bliss method. Rats were ig administrated A. vilmoriniauum and its processed products for 14 d. The chages of Ⅱ lead electrocardiogram of anesthetized rats and myocardial morphology were observed, and the serum levels of lactate kinase (CK) and lactate dehydrogenase (LDH) were detected. Results The content of yunaconitine before and after the preparation of A. vilmorinianum was 263.96 μg/g and not detected respectively. The content of 8-acetylacetonarine was not detected and 568.47 μg/g respectively. The LD₅₀ of the raw product was crude drug 4.2 g/kg, and the maximum dose of the processed product was crude drug 18.0 g/kg; In the anesthetized rats of the raw group, ventricular premature beats, ventricular bipolar law, and ventricular fibrillation occurred successively. The processed product group showed bradycardia in the early stage and returned to normal in 60 min; Compared with the blank group, the LDH and CK levels in the raw group were significantly increased (P < 0.05), and only the LDH level was significantly increased in the processed product group (P < 0.05); The gap between myocardial fibers in the raw group was significantly enlarged, and the infiltration of inflammatory cells was obvious. The myocardial fibers of the product group are arranged neatly, and individual inflammatory cells infiltrated in the interstitial. Conclusion At the given dose, A. vilmorinianum has greater cardiotoxicity, and the toxicity of A. vilmorinianum is obviously reduced after processing.

国家中医药管理局公益性行业科技专项（201507004）；广东省应用型科技研发专项（2015B020234009）；广东药科大学"创新强校工程"资助项目（2016KZDXM039）