B6-Trp53^(tm1)/NIFDC小鼠在MNU给药后的体质量、脏器质量、血液学及血生化指标的测定  

Measurement of the Body Weight,Organ Weight,Hematological and Blood Biochemical Parameters of B6-Trp53^(tm1)/NIFDC after MNU Administration

作　　者：吕建军[1] 杨艳伟[1] 李芊芊[1] 刘甦苏[2] 周舒雅[2] 霍桂桃[1] 范志云 祝清芬 国明 王三龙[1] 岳秉飞[2] 汪巨峰[1] 范昌发[2] 

机构地区：[1]中国食品药品检定研究院国家药物安全评价监测中心药物非临床安全评价研究北京市重点实验室,北京100176 [2]中国食品药品检定研究院实验动物资源研究所,北京100079 [3]山东省食品药品检定研究院,济南250101

出　　处：《实验动物科学》2016年第5期9-15,38,共8页Laboratory Animal Science

基　　金：科技部"十二五"重大新药创制专项课题资助项目(No.2012ZX09302001);中国食品药品检定研究院中青年发展研究基金(No.2014C3)

摘　　要：目的测定自主建立的p53+/-基因敲除小鼠(B6-Trp53^(tm1)/NIFDC)在N-甲基-N-亚硝基脲(N-Methyl-Nnitrosourea,MNU)给药后体质量、脏器质量、血液学及血生化指标,为临床前药物安全评价致癌性实验短期体内替代试验候选遗传修饰动物模型提供背景性数据。方法共设计4个组:阴性对照组(野生型小鼠)给予生理盐水、溶媒对照组(B6-Trp53^(tm1)/NIFDC小鼠)给予枸橼酸缓冲液、MNU组1(B6-Trp53^(tm1)/NIFDC小鼠)给予75 mg/kg MNU、MNU组2(野生型小鼠)给予75 mg/kg MNU,阴性对照组和MNU组2每组野生型小鼠各20只,雌雄各半,溶媒对照组和MNU组1每组B6-Trp53^(tm1)/NIFDC小鼠各20只,雌雄各半,测定其体质量、主要脏器质量、相对脏器质量、血液学及血生化指标,并进行统计分析。结果 MNU组1、MNU组2动物体质量降低与阴性对照组、溶媒对照组相比都存在显著性统计学差异(P<0.05)。MNU组1、MNU组2动物心脏、肝脏、脾脏、肺脏、胸腺和颌下腺的绝对质量与阴性对照组、溶媒对照组相比有显著性统计学差异(P<0.05)。MNU组1和MNU组2动物心脏、肝脏、脾脏、肺脏、肾脏、脑、胸腺和颌下腺的相对质量与阴性对照组、溶媒对照组相比有显著性统计学差异(P<0.05)。MNU组1和MNU组2动物均发现NEU、LYM%、LUC%、RBC、HGB、HCT、MCV、MCHC、RDW、HDW、CHCM、CHDW、PDW、MPV及PLT等15个指标与阴性对照组和溶媒对照组相比有显著性统计学差异(P<0.05)。另外,MNU组1和MNU组2均发现TP、ALB、CREA、UREA、TCHO、TG、CA等7个指标与阴性对照组和溶媒对照组有显著性统计学差异(P<0.05),MNU组2的AST与阴性对照组和溶媒对照组有显著性升高(P<0.05),但MNU组1和MNU组2组间没有显著性统计学差异。结论本文测定并分析了自主建立的p53+/-基因敲除小鼠(B6-Trp53^(tm1)/NIFDC)和野生型小鼠分别给予MNU及枸橼酸缓冲液后的体质量、脏器质量、血液学及血生化指标,该模型有望将来�Objective To determine body weight,organ weight,hematological and blood biochemical parameters of p53 ＋/-gene knockout mice,constructed by us and named as B6-Trp53tm1/NIFDC,after MNU administration of MNU and to provide background data for candidate animal models used as short-term in vivo alternative carcinogenicity study in the field of preclinical safety evaluation of drugs. Method There were four different groups,negative control group： wild type C57 BL/6 mice treated with saline solution; vehicle control group： B6-Trp53tm1/NIFDC mice treated with citrate buffer solution; MNU group 1： B6-Trp53tm1/NIFDC mice treated with75 mg/kg MNU and MNU group 2： wild type C57 BL/6 mice treated with 75 mg/kg MNU. Both negative control group and MNU group 2 have 20 wild type animals,10 male 10 female. Both vehicle control group and MNU group1 have 20 B6-Trp53tm1/NIFDC mice,10 male 10 female. The body weight,absolute organ weight,relative organ weight,hematological and blood biochemical parameters were measured and carried out statistical analysis.Result The decrease of the body weight of MNU group 1 and MNU group 2 compared with negative and vehicle control groups was statistically significant（ P 〈 0. 05）. There was statistically significant difference（ P 〈 0. 05） of the absolute weight of heart,liver,spleen,lung,thymus and mandibular salivary gland of MNU group 1 and 2compared with those of the negative and vehicle control groups. Furthermore,there was also statistically significant difference（ P 〈 0. 05） of the relative weight of heart,liver,spleen,lung,kidney,brain,thymus and mandibular salivary gland of MNU group 1 and 2 compared with those of the negative and vehicle control groups. When the hematological parameters of MNU group 1 and 2 were compared with those of the 2 control groups,there were statistically significant difference（ P 〈 0. 05） in 15 parameters,including NEU,LYM%,LUC%,RBC,HGB,HCT,MCV,MCHC,RDW,HDW,CHCM,CHDW,PDW,MPV and PLT. When the blood biochemical parameters of MNU gro

关 键 词：p53+/-基因敲除小鼠 脏器质量 血液学指标 血生化指标 

分 类 号：R-332[医药卫生]