目的 通過N-甲基亞硝基脲（MNU）誘導(dǎo)p53^+/-小鼠產(chǎn)生胸腺T淋巴母細(xì)胞淋巴瘤（T-LBL）。方法 采用單次ip給予p53^+/-小鼠75 mg·kg^-1 MNU，并于給藥后進(jìn)行一般癥狀觀察、攝食量及體質(zhì)量測定；給予MNU 10周后全自動生化分析儀檢測血清堿性磷酸酶（ALP）、乳酸脫氫酶（LDH）水平；解剖后進(jìn)行大體檢查，HE染色后進(jìn)行胸腺組織病理學(xué)檢查；免疫組化檢測胸腺CD20、CD3、CD68表達(dá)。結(jié)果 與對照組比較，p53^+/-小鼠的攝食量和體質(zhì)量降低（P＜0.05、0.01），第9～10周可見消瘦、弓背及呼吸急促癥狀，甚至動物死亡；血清ALP明顯降低（P＜0.01），LDH明顯升高（P＜0.01）；大體病理學(xué)檢查胸腺體積增大，呈淺黃白色，鏡檢可見胸腺惡性淋巴瘤；免疫組化檢測胸腺惡性淋巴瘤CD3和CD68呈陽性表達(dá)，CD20呈陰性表達(dá)。結(jié)論 單次給予75 mg·kg^-1 MNU可誘導(dǎo)p53^+/-小鼠產(chǎn)生胸腺惡性淋巴瘤，且為T細(xì)胞來源，其形態(tài)學(xué)與免疫學(xué)特征與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

中國食品藥品檢定研究院關(guān)鍵技術(shù)研究基金(課題編號：GJJS-2022-6-5);國家“重大新藥創(chuàng)制”科技重大專項資助項目(2018ZX09201-017)#共同