半乳糖化白蛋白磁性阿霉素纳米粒静脉给药的急性毒理实验

目的研究半乳糖化白蛋白磁性阿霉素纳米粒(Galactosed human serum Albumin Magnetic Adriamycin Nanoparticles,GAMANP)经外周静脉用药的药物毒性.探索其半数致死量,比较其与阿霉素对大鼠血液生化和外周血细胞的影响及用药后心、肝、肺、肾、肠的病理表现.反复给药观察动物对该药物有无过敏反应.方法将给GAMANP的动物分为8个剂量组,每组SD大鼠10只,观察静脉给药后急性毒性试验LD50.同时设定的空白对照组和阿霉素(Adriamycin ADM)组(6组),每组10只.观察给药后各组实验大鼠的生存情况,外周血细胞的改变和血液生化及心、肝、肺、肾等脏器的病理学变化.采用Bliss法计算LD50.SPSS(11.5)统计软件统计GAMANP和阿霉素对大鼠的外周血细胞和生化指标(肝、肾功能、心肌酶学)的影响.另选同批大鼠20只分为2组,每组10只.腹腔注射GAMANP 3次后,再次皮下注射GAMANP,观察有无过敏现象发生.结果GAMANP的动物半数致死量为515.5 mg/kg(相当阿霉素22.84 mg/kg).阿霉素半数致死量为10.38 mg/kg.前者较后者有明显的增高.同时肝、肾功能的损害和心肌酶学的改变也明显减轻.光学显微镜下的病理损害表现也明显的减轻.20只动物进行过敏实验,观察到一只动物有过敏现象.结论GAMANP是一种很好的新型改进性药物,它经过修饰后,明显的减轻了药物对心脏,肾脏和心脏的毒损作用.有望批量生产,在临床上推广试用.

Study of acute toxicity of galactosed human serum albumin magnetic adriamycin nanoparticles for rats

Objective: To study the acute toxicity of Galactosed human serum Albumin Magnetic Adriamycin Nanoparticles (GAMANP) for rats by injected in vein. Methods: 150 animals were divided into 15 groups randomly. 8 teams were gived corresponding dose of GAMANP; 6 teams were gived corresponding dose of Adriamycin(ADM) and one team rats were gived asepsis water in vein. Then detecting median lethal dose (LD50) of the two drugs by the Bliss method; Observing blood biochemical (function of the liver and kidney; enzyme of cardiac muscle) changes of the rats and the pathological changes of heart, liver, lung, kidney and intestine; Observing changes of the blood cell number and width; Observing the irritability of the GAMANP; And observing the difference of the two kinds drug by the SPSS. Results: The LD50 of GAMANP was 515.5 mg/kg, and the LD50 of ADM was 10.38 mg/kg. Compared to ADM, GAMANP effectively reduced the changes of the blood biochemistry and pathological damage such as cardiotoxicity, hepatotoxicity, nephrotoxicity and gastroenterotoxicity. The spleen remained the same in both. The large dose of ADM can make severe damage to the body. On the contrary GAMANP is not severe. We observed the anaphylaxis on one of the 20 rats.Conclusion: GAMANP significantly diminished the toxicity of adriamycin in the important organs of the body. The LD50 of GAMANP was improved greatly than that of ADM. It is a new type of anticancer drug in the foreground in the future.