摘要目的 探讨应用人肿瘤组织块外科原位移植术及体内连续传代法建立人肝原发性淋巴瘤裸鼠模型.方法 将人原发性肝淋巴瘤术中新鲜瘤组织块采用外科原位移植术植入裸鼠肝实质内,通过鼠间连续原位传代法建立生物学特性能够完整模拟肝淋巴瘤患者的裸鼠原位移植模型.观察该模型的移植成瘤率及其侵袭、转移情况,并采用组织病理学(光镜、免疫组化)、血清学、染色体核型和流式细胞术进行分析.结果 在裸鼠体内建成人原发性肝淋巴瘤原位移植模型,命名为HLBL-0102.移植瘤组织病理学为原发性肝淋巴瘤(弥漫大B细胞性),免疫组化示CD20、CD79a和MUM1阳性.HLBL-0102模型呈甲胎蛋白阴性,HBsAg阳性,乳酸脱氢酶升高[(1223±258)比(124±54) U/L,P＜0.01].移植瘤染色体众数范围56 ～ 59条,DNA指数为1.7±0.2,为异倍体.该模型已传至42代,共移植裸鼠320只,肿瘤移植生长率和液氮冻存复苏成活率均为100％.人原发性肝淋巴瘤在裸鼠肝内自主侵袭性生长,瘤细胞侵入并破坏邻近肝组织和门脉区内胆管、静脉及动脉,无其他组织、器官侵犯及远处淋巴结累及.结论 HLBL-0102模型是成功的人肝原发性淋巴瘤裸鼠原位移植模型.

abstractsObjective To establish a nude murine model of human primary hepatic lymphoma (PHL) with surgical orthoiopic implantation of histologically intact human tumor tissue and in vivo continuous orthotopic passage.Methods Histologically intact lymphoma tissues harvested intraoperatively from a PHL patient were othotopically transplanted into liver parenchyma of nude mice and in vivo continuous orthotopic passage in nude mice was used to develop a nude murine model mimicking the biological characteristics of PHL patients.Histopathology (light microscopy and immunohistochemistry),serological test,karyotypic analysis and flow cytometry were used to explore the tumorgenecity, invasion and metastasis.Results An orthotopic nude murine model of PHL,named HLBL-0102,was successfully developed.Histopathology of transplanted tumors showed primary hepatic lymphoma ( diffuse large B cell )stained positive for CD20,CD79a and MUM1.Serological test in tumor-bearing mice indicated that alphafetal protein (AFP) was negative and hepatitis B surface antigen (HBsAg) positive.The serum level of lactate dehydrogenase ( LDH ) was elevated to an average of ( ( 1223 ± 258 ) vs ( 124 ± 54) U/L,P ＜ 0.01 ).The chromosomal number of transplanted tumors was between 55 and 59.The DNA index (DI) of 1.7 ±0.2indicated heteroploid.So far HLBL-0102 model has been passed for 42 generations in nude mice.A total of 320 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumors were both 100％.The transplanted tumors grew invasively in the liver of nude mice and destroyed adjacent liver tissues and bile ducts,veins and arteries of portal area.There was no involvement of other tissues,organs and distal lymph nodes.Conclusion An orthotopically transplanted model has been successfully established for human primary hepatic lymphoma in nude mice.