B细胞非霍奇金淋巴瘤小鼠模型的建立

Establishing SCID mouse models of B-cell non-Hodgkin's lymphoma

背景与目的:近年来非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)发病率呈上升趋势,其中侵袭性NHL占了很大的比例,然而传统化疗方案提高NHL疗效的空间有限。本研究旨在建立淋巴瘤小鼠模型,为探讨治疗NHL新方案并研究其药物作用机制提供动物模型。方法:应用人弥漫大B细胞NHL细胞株SU-DHL-4及人Burkitt淋巴瘤细胞株Daudi,经尾静脉注射入SCID小鼠体内,探索建立淋巴瘤小鼠模型的条件及特点。Daudi淋巴瘤小鼠分为对照组及美罗华治疗组,观察小鼠的发病情况及生存时间。结果:SU-DHL-4淋巴瘤小鼠在中位时间39.5d后开始发病,主要表现为精神萎靡、消瘦、竖毛、活动迟缓,于小鼠腹腔、尾部或后肢部位出现肿块,未发现肝脏、脾脏、骨髓等脏器出现淋巴瘤细胞浸润。Daudi淋巴瘤小鼠于中位时间30.5d发病,出现双后肢瘫痪,于瘫痪后9.5d左右死亡。Daudi淋巴瘤小鼠的脏器大多受淋巴瘤细胞的累及,骨髓中出现大量Daudi细胞浸润。美罗华治疗使小鼠骨髓中的Daudi细胞呈现明显的凋亡形态。对照组Daudi淋巴瘤小鼠的中位瘫痪时间及生存时间分别为30.5d及40d,美罗华治疗组的小鼠分别为52.5d及76.5d,美罗华治疗组小鼠的中位瘫痪时间及生存时间显著延长(P<0.05)。结论:应用SU-DHL-4细胞及Daudi细胞均可以成功建立B细胞NHL小鼠模型。

Background and Objective. Recently, the incidence of non- Hodgkin＇s lymphoma （NHL） is increasing, in which most are aggressive. It is limited for promoting the efficacy of conventional chemotherapy on NHL. In this study, mouse models of B-cell NHL were established for determining the efficacy and mechanisms of novel therapies. Methode： Diffuse large B-cell lymphoma SU-DHL-4 cells and Burkitt＇s lymphoma Daudi cells were injected into SCID （severe combined immunodeficiency） mice through the tail veins to observe the presentations and requirements for establishing mouse models. The Daudi-cell lymphoma mice were divided into control group and ribuximab group, and the latter received treatment of rituximab. The tumor onset and survival time of mice were investigated. Results.. The median onset time of SU-DHL-4-cell NHL in SCID mice was 39.5 days, which presented cachexia, weight loss, erect hair, tardiness, and enlarged tumors in the abdomen, rump or pelvic limb, but without tumor cell infiltration in the liver, spleen or bone marrow. The median onset time of Daudi-cell NHL in SCID mice was 30.5 days, which were characterized by paralyzed lower limbs and died about 9.5 days after paralysation. Most organs such as the liver, kidney, spleen and bone marrow were infiltrated by a number of Daudi cells. After treatment of rituximab, Daudi cells presented typical characters of apoptosis. The median paralysation time and survival time of mice with Daudi-cell NHL were significantly longer in rituximab group than in control group （52.5 days vs. 30.5 days, 76.5 days vs. 40 days, P〈0.05）. Conclusion： SCID mouse models of B-cell NHL can be successfully established with either SU-DHL-4 cells or Daudi cells.