冰川棘豆生物碱对小白鼠的毒性研究

Toxicity of Alkaloids Isolated from Glacial Crazyweed (Oxytropis glacialis Benth ex bye) in Mice

将冰川棘豆生物碱粗提物、生物碱结晶Ⅱ和生物碱结晶Ⅰ即 2 ,2 ,6 ,6 四甲基 4 哌啶酮 (TMPD)分别给小鼠腹腔注射 ,结果表明 ,它们具有相似的急性毒性 ,症状为活动减少 ,闭目 ,不安 ,震颤 ,惊厥 ,呼吸困难和死亡。小鼠口服TMPD的LD50 为 935 4mg/kg ,95 %可信限为 85 2 7～ 10 2 1 4mg/kg ,用每日 2 0 0 ,30 0和 40 0mg/kg剂量TMPD灌胃小鼠 ,30d左右出现目光呆滞 ,被毛粗乱 ,卧地 ,头部上下颤震 ,蹒跚行走等轻微的疯草中毒症。 35d时进行检查发现 ,主要病理变化为肝脏、大脑和小脑空泡变性。此外 ,中央静脉、小叶间静脉和叶下静脉以及肝窦隙扩张淤血 ,有的肝细胞肿大或轻度溶解 ,胞内出现多数红色细小颗粒 ,胞核大小和染色不一 ,窦壁细胞轻度肿胀增生 ;小脑蒲肯野氏细胞不同程度溶解 ,尼氏小体减少 ;大脑出血 ,胞核固缩。

The basic material,crystall Ⅱ and crystal Ⅰ,2,2,6,6-tetramethyl-4-piperidone(TMPD)got from Oxytropis glacidalis ,all had similar acute toxicity to mice by intraperitoneal injection and the poisoned mice had signs of listlessness,closed eyes,uneasiness,tremor,convulsions,breath with difficulty and death.The oral medium lethal dose of TMPD in mice was 935.4 mg/kg with 95% confidence limit 852.7～1 021.4 mg/kg.Mice were individually fed with TMPD at dosages of 200,300 and 400 mg/kg once a day respectively.After approximately 30 days of feeding,the mice developed mild clinical signs of locoweed intoxication which included central nervous system depression,roughened coat,halting walk,dullness,lusterless eyes,and loss of weight.On the 35th day,all mice were killed and their liver,cerebrum and cerebellum tissue samples were taken for microscopic examination.Tissues were fixed and prepared according to standard histology procedures.Cytoplasm vacuolation was observed in all tissues collected from the mice that were fed TMPD,together with some other pathologic changes:cental veins,small veins between lobuli,veins beneath lobes and sinusoids of liver expanded and congested.Some liver cells dissoloved slightly,others enlarged and a great number of small red grains appeared in it.Some nuclei of the liver cells dissolved or disappeared and some sinus wall cells swollen and hyperplasia slightly.The Purkinje cells of cerebellum swelled,dissolved incompletely or completely.The dyeing abilities of their cytoplasm and nuclei declined or ascended.The numbers of Nissl bodies decreased;the pathologic changes of cerebrum were similar to those of cerebellum,with pyhnosis and hemorrhage.