目的 考察生川乌醇提物致心、脑毒性的表现和对血管内皮细胞的影响。方法 雄性Wistar大鼠随机分为对照组、生川乌醇提物低、中、高剂量（2.5、5.0、7.5 g/kg）组，连续ig给药15 d。观察大鼠毒性反应和死亡情况，并于给药结束后检测心电图，采集血液进行血常规和血生化分析。处死后取脑测定脏器系数并进行病理检查；取左心室和海马区组织块做电镜观察。结果 给药结束时生川乌高剂量组大鼠全部死亡，生川乌中剂量组死亡率显著升高，血液中红细胞计数（RBC）、血红蛋白（HGB）、红细胞容积（HCT）、丙氨酸转氨酶（ALT）、尿素（UREA）、葡萄糖（GLU）显著增高；低、中剂量组均出现各种心律失常，其中室性心律失常最为明显。生川乌中剂量组动物脑指数明显增加，局灶性海马区神经元固缩明显增多。电镜观察结果表明，生川乌中剂量组局部海马区神经元胞质溶解、核碎裂，胶质细胞凝固性坏死；左心室和海马区血管内皮细胞明显损伤、凋亡。结论 在所给剂量下，生川乌醇提物能造成明显的心脏毒性和神经毒性，并导致血管内皮细胞损伤、凋亡。

Objective To investigate the features of cardiotoxicity and neurotoxicity and the influence on vascular endothelial of ethanol extract of Aconiti Radix (AR). Methods Totally 45 Wistar rats were randomly divided into four groups, and ig given low-, middle-, and high-dose 70% ethanol extract of AR (in the raw drug dose of 2.5, 5.0, and 7.5 g/kg respectively) for 15 d. The toxic reaction and death condition were observed during administration. The electrocardiogram (ECG) change was tested after administration. Blood was collected for blood routine and blood biochemistry analysis. Brain was harvested for calculating viscera index and pathological examination. Left ventricular and hippocampus were extracted and stained with electron microscope (EM) methods. Results At the end of treatment, all rats were sacrificed in the high-dose AR group. The mortality and hematologic parameters including RBC, HGB, HCT, ALT, UREA, and GLU were significantly increased in the middle-dose AR groups compared with control group. Arrhythmia especially ventricular arrhythmia occurred in low- and middle-dose AR group. Brain index and number of pyknotic neurons in focal area of hippocampus were significantly increased in middle-dose AR group. EM examination indicated that dissolution of neuronal inclusions, nuclear fragmentation, and coagulation necrosis of glial cells were prominent in the hippocampus tissue in middle-dose AR group. In the middle-dose AR group, the vascular endothelial cells injury and apoptosis were obviously observed in left ventricular and hippocampus separately. Conclusion The ethanol extract of AR can lead to cardiotoxicity and neurotoxicity especially vascular endothelial injury in dose-dependent manner.

国家重点基础研究发展计划（“973”计划）项目（2011CB505300，2011CB505302）