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。

Objective Establishment of a new malignant lymphoma model of thymus in p53^+/-mice induced by N-methyl-Nnitrosourea (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.

R965.2

中国食品药品检定研究院关键技术研究基金(课题编号：GJJS-2022-6-5);国家“重大新药创制”科技重大专项资助项目(2018ZX09201-017)#共同