药物评价研究2024,Vol.47Issue(11) :2607-2612.DOI:10.7501/j.issn.1674-6376.2024.11.016

N-甲基亚硝基脲诱导p53+/-小鼠胸腺淋巴瘤模型的建立

Establishment of a lymphoma model of thymus in p53+、-mice induced by N-methyl-N-nitrosourea

叶润泽 张勇 林志 屈哲 李双星 张頔 杨艳伟 王三龙 刘甦苏 霍桂桃
药物评价研究2024,Vol.47Issue(11) :2607-2612.DOI:10.7501/j.issn.1674-6376.2024.11.016

N-甲基亚硝基脲诱导p53+/-小鼠胸腺淋巴瘤模型的建立

Establishment of a lymphoma model of thymus in p53+、-mice induced by N-methyl-N-nitrosourea

叶润泽 1张勇 2林志 2屈哲 2李双星 2张頔 2杨艳伟 2王三龙 2刘甦苏 3霍桂桃2
扫码查看

作者信息

  • 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;中国药科大学基础医学与临床药学学院,江苏南京 211198
  • 2. 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
  • 3. 中国食品药品检定研究院实验动物资源研究所,北京 102629
  • 折叠

摘要

目的 通过N-甲基亚硝基脲(MNU)诱导p53+/-小鼠产生胸腺T淋巴母细胞淋巴瘤(T-LBL).方法 采用单次ip给予p53+/-小鼠75 mg·kg-1 MNU,并于给药后进行一般症状观察、摄食量及体质量测定;给予MNU 10周后全自动生化分析仪检测血清碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)水平;解剖后进行大体检查,HE染色后进行胸腺组织病理学检查;免疫组化检测胸腺CD20、CD3、CD68表达.结果 与对照组比较,p53+/-小鼠的摄食量和体质量降低(P<0.05、0.01),第9~10周可见消瘦、弓背及呼吸急促症状,甚至动物死亡;血清ALP明显降低(P<0.01),LDH明显升高(P<0.01);大体病理学检查胸腺体积增大,呈浅黄白色,镜检可见胸腺恶性淋巴瘤;免疫组化检测胸腺恶性淋巴瘤CD3和CD68呈阳性表达,CD20呈阴性表达.结论 单次给予75 mg·kg-1 MNU可诱导p53+/-小鼠产生胸腺恶性淋巴瘤,且为T细胞来源,其形态学与免疫学特征与T-LBL相似.

Abstract

Objective Establishment of a new malignant lymphoma model of thymus in p53+、-mice induced by N-methyl-N-nitrosourea(MNU).Methods Administration of 75 mg·kg-1 MNU to p53+/-mice via a single ip,followed by general symptom observation,food intake,and body mass measurement after administration.After 10 weeks of treatment with MNU,the levels of serum alkaline phosphatase(ALP)and lactate dehydrogenase(LDH)were measured using a fully automated biochemical analyzer;Perform gross examination after dissection,and perform histopathological examination of thymus tissue after HE staining;Immunohistochemical detection of CD20,CD3,CD68 expression in thymus.Results Compared with the control group,the food intake and body weight of p53+/-mice decreased(P<0.05,0.01),and symptoms such as emaciation,hunchback,and shortness of breath were observed in weeks 9-10,even leading to animal death.Serum ALP significantly decreased(P<0.01)and LDH significantly increased(P<0.01).Gross pathological examination showed an increase in thymus volume,appearing pale yellow white,and microscopic examination revealed malignant lymphoma of the thymus;Immunohistochemical detection showed positive expression of CD3 and CD68 in thymic malignant lymphoma,while CD20 showed negative expression.Conclusion Single intraperitoneal injection of 75 mg·kg-1 MNU can induce thymus malignant lymphoma in p53+/-knockout mice,and the tumor was derived from T cells and the morphological and immunological characteristics were similar to human T-LBL.

关键词

N-甲基亚硝基脲/p53+/-敲除小鼠/胸腺/T淋巴母细胞淋巴瘤/模型建立

Key words

N-methyl-N-nitrosourea/p53+/-mice/thymus/T lymphoblastic lymphoma/model establishment

引用本文复制引用

出版年

2024
药物评价研究
天津药物研究院 中国药学会

药物评价研究

CSTPCD北大核心
影响因子:1.199
ISSN:1674-6376
段落导航相关论文