体内连续筛选法建立人原发性小肠恶性淋巴瘤裸鼠原位移植肝转移模型  

Reproduction of a murine model of liver metastasis of human primary malignant lymphoma of small intestine by continuous screening in vivo

作　　者：脱朝伟[1] 刘秋珍[1] 张宁[1] 杨波[1] 王明耀[1] 魏强[1] 

机构地区：[1]解放军第202医院电子显微镜室,沈阳110003

出　　处：《解放军医学杂志》2007年第9期926-929,共4页Medical Journal of Chinese People's Liberation Army

基　　金：国家重点科技攻关项目(96-A23-06-03);辽宁省自然科学基金资助项目(20042153)

摘　　要：目的采用人原发性小肠恶性淋巴瘤肝转移灶建立人小肠恶性淋巴瘤裸鼠原位移植肝转移模型,为探讨小肠恶性淋巴瘤肝转移机制提供动物模型。方法将人小肠恶性淋巴瘤肝转移灶的新鲜组织块植入裸鼠小肠黏膜层内,成瘤后的肝转移灶移植至另一裸鼠小肠黏膜层内,在裸鼠体内重复进行4次肝转移筛选,取肝转移灶再进行裸鼠小肠移植。观察原位移植成瘤率,移植瘤的侵袭和肝转移率,进行形态学(光镜、电镜、免疫组织化学)、染色体核型和流式细胞分析。结果由小肠恶性淋巴瘤肝转移灶成功建成人原发性小肠恶性淋巴瘤裸鼠原位移植肝转移模型(命名为HSIL-0402)。该移植瘤组织病理学分型为非霍奇金淋巴瘤(弥漫型大细胞淋巴瘤,B细胞性)。免疫组织化学显示CD19、CD20、CD45、CD79a阳性,CD3、CD7阴性。染色体众数56～69条,流式细胞DNA指数(DI)值1.61±0.37,均为异倍体。HSIL-0402已经传至27代,共移植裸鼠156只,肿瘤的移植生长率、肝转移率和液氮冻存复苏成活率均为100%。淋巴结转移率为67.4%,腹腔种植转移率为61.7%。人小肠恶性淋巴瘤在裸鼠小肠内自主侵袭性生长,并发生血液转移、淋巴转移和腹腔内种植性转移。结论首次成功地建立了人小肠恶性淋巴瘤裸小鼠原位移植自发性肝转移模型HSIL-0402,为研究小肠恶性淋巴瘤肝转移生物学机制和抗转移治疗提供动物模型。Objective A liver metastasis model of human primary malignant lymphoma of small intestine was reproduced in nude mice in an attempt to provide an ideal animal model for elucidating the mechanism of liver metastasis of primary small intestinal lymphoma. Methds A piece of surgically obtained liver metastatic tissue of small intestinal lymphoma was implanted into the mucous membrane of small intestine in nude mice to reproduce the model. After metastasis of this tumor to the liver occurred, a portion of the metastais was transplanted into the mucous membrane of small intestine of another nude mouse. This process was repeated 4 times in order to obtain a cell line with the characteristics of high malignant lymphoma metastasis to liver. The survival rate of the experimental animals, regional invasion rate and metastasis rate were observed, and the morphological characteristics （light microscopy, electron microscopy and immunohistochemistry）, karyotype analysis and DNA content of the neoplastic cells were also determined. Results A liver metastasis model of human primary malignant lymphoma of small intestine in nude mice （termed HSIL-0402） was successfully reconstructed, by repeated implantation of liver metastatic tumor in vivo. Histopathology showed HSIL-0402 tumor was a high grade non-Hodgkinrs lymphoma. Immunohistology showed the cells were CD19, CD20, CD45 and CD79a positive, but negative for CD3 and CDT. The modal number of chromosome was between 56--69. DNA index （DI） was 1. 614-0. 37, which showed heteroploid. So far, HSIL-0402 had been maintained for 27 passages in nude mice, exhibiting 100% of transplantability, liver metastatic rate, and resuscitation rate after liquid nitrogen cryopreservation. Lymph node metastasis and celiac seeding occurred in 67.4% and 61. 7% of a total of 156 observed animals. The HSIL-0402 model displayed various manifestations reminiscent of highly metastatic invasive behavior in nude mice, including invasive growth, hematogenous metastasis, lymph node metastasis and celi

关 键 词：肠肿瘤 淋巴瘤 肿瘤移植 肿瘤转移 疾病模型 动物 

分 类 号：R733.41[医药卫生—肿瘤]