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目的:观察犬长期应用复方樟柳碱注射液的中毒反应及可逆性,寻找中毒的靶器官。方法:选用一级Beagle犬16只,雌雄各半,随机分4组。分别设为生理盐水对照组、复方樟柳碱4.04、40.4和121.2mg/kg/d组。在连续皮下注射给药2个月后,各组分别处死2只动物,余下动物停药并继续观察1个月后处死。结果:121.2mg/kg/d组动物表现出精神沉郁、甚至沉睡,呕吐、流涎,后肢麻痹,以及有时给药后抽搐、瞳孔散大。在给药期结束时,可见脑电图振幅变小,周期也呈变慢的趋势。超微结构观察可见大脑神经细胞缺氧性变性、坏死变化,以及神经胶质细胞胞浆溶酶体、次级溶酶体增多。停药后毒性反应消失,损伤可修复。40.4mg/kg/d组动物给药后可见精神沉郁或兴奋、流涎及有时呕吐。停药后毒性反应迅速消失。4.04mg/kg/d组及对照组动物未见明显异常。结论:中枢神经系统是复方樟柳碱的毒性靶器官之一,40.4mg/kg/d为轻度中毒剂量,121.2mg/kg/d为中毒剂量。
Objective: To observe the long-term application of compound anisodine injection poisoning reaction and reversibility, looking for poisoning target organ. Methods: Choose a Beagle dog 16, male and female, randomly divided into 4 groups. They were set as normal saline control group, compound anisodine 4.04,40.4 and 121.2mg / kg / d group respectively. Two months after continuous subcutaneous injection, two animals were sacrificed in each group, and the remaining animals were discontinued and observed one month later. Results: The animals at 121.2 mg / kg / d showed depression, even asleep, vomiting, salivation, paralysis of the hind limbs, convulsions after administration, and mydriasis. At the end of the dosing period, it can be seen that the amplitude of the EEG becomes smaller and the period of the EEG tends to be slower. Ultrastructural observation showed that cerebral neurons hypoxic degeneration, necrosis changes, as well as glial cytoplasmic lysosomes, secondary lysosomes increased. Toxicity disappeared after treatment, injury can be repaired. 40.4mg / kg / d group of animals can be seen after administration of depression or irritability, salivation and sometimes vomiting. Toxicity disappeared rapidly after withdrawal. 4.04mg / kg / d group and the control group animals showed no abnormalities. Conclusion: The central nervous system is one of the toxic target organs of compound anisodine, 40.4mg / kg / d is mild toxic dose, 121.2mg / kg / d is toxic dose.