Abstract: Abstract: 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 C57BL /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 with 75 mg /kg MNU and MNU group 2: wild type C57BL /6 mice treated with 75mg /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 group 1 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 2 compared 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 group 1 and 2 were compared with those of the 2 control groups，there were statistically significant difference ( P ＜ 0. 05) in 7 parameters，including TP，ALB，CＲEA，UＲEA，TCHO，TG and CA． AST was only statistically significant higher in MNU group 2 compared with that of the 2 control groups ( P ＜ 0. 05) ．There was no statistically significant difference between MNU group 1 and MNU group 2． Conclusion The body weight，organ weight，hematological and blood biochemical parameters of B6 － Trp53tm1 /NIFDC mice and wild type mice treated with MNU or citrate buffer solution were measured and analyzed in the paper． The model might be used as a short-term in vivo alternative carcinogenicity study in the field of preclinical safety evaluation of drugs in the future．

Key words: <p>p53 + / － gene knockout mice, organ weight, hematological parameters, blood biochemical parameters</p>

摘要： 摘要: 目的测定自主建立的p53 + / － 基因敲除小鼠( B6-Trp53tm1 /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-Trp53tm1 /NIFDC 小鼠) 给予枸橼酸缓冲液、MNU 组1 ( B6-Trp53tm1 /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-Trp53tm1 /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-Trp53tm1 /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，该模型有望将来用于临床前药物安全评价致癌性实验短期体内替代试验。

关键词: <, p>, p53 + / － 基因敲除小鼠, 脏器质量, 血液学指标, 血生化指标<, /p>