蝎毒抗癌多肽及其纯化组分Ⅰ及Ⅲ的毒性观察

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目的 :观察蝎毒抗癌多肽 (APBMV)纯化组分Ⅰ (AP Ⅰ )及Ⅲ (AP Ⅲ )与蝎毒抗癌多肽之间的毒性差别 ,为前二者药效学研究提供新的实验依据。方法 :取昆明种小鼠 180只 ,随机分为 18组 ,每组 10只 ,腹腔一次注射0 .2ml/ 2 0g不同浓度的APBMV(1~ 6组 )、AP Ⅰ (7~ 12组 )及AP Ⅲ (13~ 18组 ) ,观察动物的行为学改变 ,并取出死亡动物脏器进行病理学观察 ,按照综合计算法得出AP Ⅰ、AP Ⅲ与APBMV的LD50 和 95 %可信区间。结果 :小鼠注射高浓度的APBMV、AP Ⅰ或AP Ⅲ后 ,在 2min后即出现明显的烦躁、尖叫、嘶咬、多涎 ,继而呆滞、呼吸不规则、颈毛直立等行为学改变 ,随着给药时间的延长 ,动物会表现行动迟缓、竖尾、腹泻、喘息性呼吸 ,后肢强直 ,窒息直至死亡。而其他各组在 3min后才出现程度不同的毒性反应。高浓度组动物在 2 5min内全部死亡 ,其他各组部分动物在 6 0min内相继死亡。死亡和处死动物内脏无明显病理学改变。APBMV、AP Ⅰ或AP Ⅲ的LD50 和 95 %可信区间分别为 1.386 ,1.118,1.145和 (1.386± 0 .2 47) ,(1.118± 0 .194) ,(1.145± 2 0 .198)。结论 :APBMV经进一步纯化后 ,其有效成分AP Ⅰ及AP Ⅲ毒性均有显著提高 OBJECTIVE: To observe the difference in toxicity between APBMV purified components I (AP I) and III (AP III) and scorpion venom anti-cancer polypeptides, providing a new experimental basis for the study of pharmacodynamics of the former two drugs. . METHODS: A total of 180 Kunming mice were randomly divided into 18 groups with 10 mice in each group. One intraperitoneal injection of 0. 2 ml / 20 g APBMV (1 to 6 groups) and AP I (7 to 12 groups) at different concentrations was performed. AP III (13-18 groups) observed animal behavioral changes, and removed the dead animals organ for pathological observation. The LD50 and 95% confidence intervals for AP I, AP III, and APBMV were calculated according to a comprehensive calculation method. RESULTS: After the mice were injected with high concentrations of APBMV, AP I or AP III, obvious irritation, screaming, biting, and paralysis occurred after 2 minutes, followed by behavioral changes such as sluggishness, irregular breathing, and upright erection of the neck hair. With the extension of the administration time, the animals will show sluggishness, vertical tail, diarrhea, wheezing breathing, hind limb rigidity, and suffocation until death. The other groups showed toxic reactions with different degrees after 3 minutes. Animals in the high-concentration group all died within 25 minutes, and some other animals in each group died within 60 minutes. No significant pathological changes were observed in the viscera of animals that died or were sacrificed. The LD50 and 95 % confidence intervals for APBMV, AP I or AP III were 1.386, 1.118, 1.145 and (1.386 ± 0.247), (1.118 ± 0 .194), (1.145 ± 2 0.198), respectively. Conclusion : After the APBMV was further purified, the toxicities of its active ingredients AP I and AP III were significantly improved.
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