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目的 研究N-甲基-N-亚硝基脲(N-Methyl-N-Nitrosourea,MNU)诱导Tg.C57-ras转基因小鼠模型杂交一代及其同窝野生型小鼠产生的胸腺肿瘤的病理特点及免疫分型，初步探索构建淋巴瘤动物模型的可行性。方法 MNU以75 mg/kg·bw的剂量单次腹腔注射43只Tg.C57-ras转基因小鼠(雌性21只，雄性22只)及40只同窝野生型小鼠(雌雄各20只)。将26周试验结束时收集到的Tg.C57-ras转基因小鼠及同窝野生型小鼠的胸腺肿瘤组织及其他主要脏器取材，制作组织切片，进行苏木素-伊红(hematoxylin-eosin,HE)染色及免疫组织化学实验。结果 光学显微镜下胸腺肿瘤表现出以下特征:胸腺正常结构被肿瘤组织破坏，肿瘤细胞形态单一，细胞核大而细胞质少，核质比高，星空现象和核分裂象多见。免疫组化结果显示肿瘤细胞CD3、PCNA及Td T呈现出阳性表达，CD20、CD10、PD1、CXCL13及Bcl6呈现出阴性表达。结论 MNU诱导Tg.C57-ras转基因小鼠及其同窝野生型小鼠产生的胸腺肿瘤为T细胞来源的淋巴母细胞淋巴瘤，其组织病理表现及免疫组化结果与人类T细胞淋巴母细胞淋巴瘤(T-cell lymphoblastic lymphoma,T-LBL)具有高度相似性，初步证实了C57-ras转基因小鼠适宜作为研究T-LBL肿瘤发生机制的动物模型。
Abstract：Objective To study the pathological characteristics and immunophenotyping of thymic tumors induced by N-Methyl-NNitrosourea( MNU) in the first-generation hybrid and littermate negative mice of Tg.C57-ras transgenic mice,and to preliminarily explore the feasibility of constructing a lymphoma animal model. Methods Forty-three C57-ras transgenic mice( 21 females and 22 males) and 40littermate negative control mice( 20 females and 20 males) were given MNU at a dose of 75 mg/kg·bw via a single intraperitoneal injection.Following the 26-week experimental period,thymic tumor tissues and other major organs were collected from Tg.C57-ras transgenic mice and littermate negative control mice. The tissues were processed to make tissue sections,which were then subjected to HE staining and immunohistochemical experiments. Results Histopathological study showed that the thymic tumors disrupted the normal thymic architecture,with tumor cells exhibiting a uniform type,large nuclei,scant cytoplasm and a high nucleus-to-cytoplasm ratio. The starry sky phenomenon and frequent mitotic figures were also frequently noted. Immunohistochemical analysis revealed positive expression of CD3,PCNA and Td T in the tumor cells,while CD20,CD10,PD1,CXCL13,and Bcl6 showed negative expression. Conclusion The thymic tumors induced by MNU in Tg.C57-ras transgenic mice and their littermate negative mice were T-cell-derived lymphoblastic lymphomas. The histopathological features and immunohistochemical profiles closely resembled those of human T-cell lymphoblastic lymphoma( T-LBL). These findings preliminarily validate the use of Tg.C57-ras transgenic mice as an appropriate animal model for studying the tumorigenesis mechanism of TLBL.
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基本信息:
DOI：10.16421/j.cnki.1002-3127.2025.04.005
中图分类号:R736.3
引用信息:
[1]马梦歌,敬海明,聂燕敏,等.N-甲基-N-亚硝基脲引起Tg.C57-ras转基因小鼠胸腺淋巴瘤免疫分型研究[J].毒理学杂志,2025,39(04):240-247.DOI:10.16421/j.cnki.1002-3127.2025.04.005.
基金信息: