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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 performance of Cordyceps sinensis ethanol extract on heart and brain toxicity and its effect on vascular endothelial cells. Methods Male Wistar rats were randomly divided into control group, low, medium and high dose (2.5, 5.0, 7.5 g / kg) of Wuchuanwu alcohol extract, continuous ig administration for 15 days. The toxicity and death of rats were observed, and the electrocardiogram (ECG) was measured after administration. The blood was collected for blood routine and blood biochemical analysis. After sacrifice, take the brain to determine the organ coefficient and pathological examination; take the left ventricular and hippocampus tissue slices to do electron microscopy. Results All the rats in Shengchuanwu high-dose group died at the end of administration, the mortality of middle-dose group was significantly increased, the RBC, HGB, HCT, ALT, URE and GLU increased significantly; all kinds of arrhythmia appeared in low and middle dose groups, of which ventricular arrhythmia was the most obvious. Shengchuanwu medium dose group of animal brain index increased significantly focal neurons in focal hippocampal area increased significantly. The results of electron microscopy showed that the neurons in the local hippocampus of Shengchuanwu middle dose group were cytosol lytic, nuclear fragmentation and glial cell coagulation necrosis; the vascular endothelial cells in the left ventricle and hippocampus were obviously damaged and apoptotic. Conclusions At the given doses, the extract of Radix Aconiti Kusnezoffii can cause obvious cardiotoxicity and neurotoxicity, and lead to vascular endothelial cell injury and apoptosis.