蝎毒抗癌多肽及其纯化组分Ⅰ及Ⅲ的毒性观察  

Observation of the toxicity of APBMV and AP-Ⅰ,AP-Ⅲ from APBMV

作　　者：韩雪飞[1] 林华生[2] 陈华艳[1] 郭进武[1] 董伟华[1] 孔天翰[1] 

机构地区：[1]河南医科大学生物毒素中心,郑州450052 [2]吴川市人民医院,吴川524400

出　　处：《河南医科大学学报》2001年第6期659-661,共3页Journal of Henan Medical University

基　　金：河南省科技攻关资助项目 95 12 0 0 10 2

摘　　要：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APAim:To apply antineoplastic polypeptide from Buthus martensii venom(APBMV) and its composition antineoplastic polypeptide Ⅰ(AP Ⅰ) and antineoplastic polypeptide Ⅲ(AP Ⅲ) to clinical treatment at maximum safe degree,and to evaluate the toxicosis medicinalis and side effect Methods:A total of 180 mice were randomly divided into 18 groups(10 mice/groups)Group 1～6 were injected by ip with APBMV, Group 7～12 and Group 13～18 were injected AP Ⅰ and AP Ⅲ 0.2 ml/20 g of different concentrations respectirely. The conduct and pathological changes in organs of animals were observed after the injection. The LD 50 and L95 of APBMV, AP Ⅰ and AP Ⅲ were evaluated by the method of complex count. Results: Two min after injected higher concentration AP Ⅰ,AP Ⅲ and APBMV , the changes of animal behaviors were found from screaming , jumping, lapping the injected position, slobbering to irregular breath. With the prolongation of survival time, the animals were quiescent, spastic paralystic, breathed quickly, stifled, and were convulsive until dead. Most animals died 60 min after injection, and the pathological change was not found in important internal organs of dead animals. According to the drug and death rate, the LD 50 of AP Ⅰ,AP Ⅲ and APBMV were 1.118 mg/kg,1.145 mg/kg and 1.386 mg/kg respectively,and L95 were (1.118±0.194), (1.145 ±0.198) and (1.386± 0.247) respectively. Conclusion: The LD 50 of purified AP Ⅰ and AP Ⅲ separated from APBMV is significantly higher.

关 键 词：蝎毒抗癌多肽 LD50 纯化组分 AP-I AP-Ⅲ 

分 类 号：R917[医药卫生—药物分析学] R979.1[医药卫生—药学]