蝎毒抗癌多肽与其组分Ⅲ的毒性比较  

Comparison of the toxicity of APBMV and its composition AP Ⅲ

作　　者：董伟华[1] 韩雪飞[1] 郭进武 陈华艳[1] 薛传安 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]洛阳高等医学专科学校化学教研室,洛阳471003 [3]安徽省青阳县硫铁矿医院,青阳241037

出　　处：《河南医科大学学报》2000年第4期285-288,共4页Journal of Henan Medical University

基　　金：河南省"九五"科技攻关项目!95 12 0 0 10 2

摘　　要：目的 :综合评价蝎毒抗癌多肽 (antineoplasticpolypeptidefromButhusmartensiivenom ,APBMV)及其纯化组分Ⅲ (antineoplasticpolypeptide ⅢfromAPBMV ,AP Ⅲ )毒、副作用及临床使用的安全性 ,为进一步开发、利用蝎毒抗癌制剂提供有价值的实验依据。方法 :取 2 0～ 2 2g昆明种小鼠 1 2 0只 ,雌雄各半 ,随机分为 1 2组 ,每组 1 0只 ,经小鼠腹腔一次注射 0 .2ml/ 2 0g不同浓度的APBMV(1～ 6组 )或AP Ⅲ (7～ 1 2组 ) ,观察各组动物的行为学改变和各脏器的病理变化 ,利用LD50 综合计算法得到APBMV及AP Ⅲ的LD50 及 95 %可信区间。结果 :小鼠注射大剂量的APBMV或AP Ⅲ 1～ 5min后 ,可出现尖叫不安、跳跃、舔注射部位、多涎、呆滞、呼吸不规则、颈部立毛等行为学的改变 ,随着给药时间的延长 ,动物呈俯伏不动 ,后肢痉挛性麻痹 ,呼吸加速 ,窒息 ,惊厥直至死亡 ,大部分动物的死亡时间均在注射后 90min之内。解剖死亡动物 ,心、大脑等脏器切片未见明显的病理改变。根据各组的给药剂量及死亡率 ,测得APBMVLD50 为 9.738mg/kg ,95 %可信区间为 (9.738± 1 .5 2 7)mg/kg ,AP ⅢLD50 为 8.1 77mg/kg ,95 %可信限为(8.1 77± 1 .2 79)mg/kg。结论 :AP Ⅲ的LD50 <APBMV的LD50 。Aim:In order to apply antineoplastic polypeptide from Buthus Martensii venom(APBMV) and antineoplastic polypeptide Ⅲ from APBMV(AP Ⅲ) to clinical treatment at maximum safe degree, and to evaluate the toxicosis medicinalis and side effect. Methods: 120 mice(20～22 g) were divided at random into 12 groups(10 mice/group), and injected by ip with APBMV(Group1～6) or AP Ⅲ(Group7～12) in 0.2 ml/20 g of different concentrations. The conduct and pathological changes in organs of animals were observed after drug injected.The LD 50 and L 95 of APBMV or AP Ⅲ were evaluated with the method of complex count. Results: 1～5 min after injecting APBMV or AP Ⅲ in higher concentration, the changes of animal behaviours 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 were dead in 90 min after injection and then anatomized. The pathological change was not found by naked eye in important internal organs of dead animals. According to the drug and dead rate, the LD 50 of APBMV was 9.738 mg/kg and L 95 was from 8.211 mg/kg to 11.265 mg/kg,the LD 50 of AP Ⅲ was 8.17 mg/kg and L 95 was from 6.898 mg/kg to 9.456 mg/kg. Conclusion: The LD 50 of AP Ⅲ is lower than APBMV’s, which means the acute toxicity of the former is higher than that of the latter.

关 键 词：蝎毒抗癌多肽 AP-Ⅲ 毒性 副作用 安全性 

分 类 号：R979.1[医药卫生—药品]