免疫重建荷人卵巢癌严重联合免疫缺陷鼠腹腔移植模型的建立

目的：建立免疫重建的荷人卵巢小鼠腹腔移植模型。方法：用人外周血淋巴细胞（PBL悬液腹腔注射建立有免疫功能的严重联合免疫缺陷（SCID）鼠模型3只;用人PBL和人卵巢癌细胞株SKOV3细胞腹腔注射建立免疫重建荷人卵巢癌SKOV3 SCID鼠模型3只,观察其生物学、免疫学特性。结果：每组免疫重建小鼠成瘤比例为3／3。免疫重建均检测到人IgG 存在,与未重建组比较差异有显著意义（P＜0．05）;免疫重建荷瘤鼠主要成瘤在腹腔,分布于肝下素、腹膜、横膈、肠系膜等部位,与未重建组比较,成瘤减少;原代移植瘤细胞形态、CA125表达与SKOV3细胞相似,但透射电镜观察到早期细胞凋亡表现;组织学观察到成片淋巴细胞浸润。结论：免疫重建荷人卵巢癌SCID鼠腹腔移植模型已初步建立,本模型较好地模拟了在免疫功能情况下人卵巢癌腹腔播散的生物学行为,为卵巢癌治疗的临床前研究提供了较理想动物模型。

Development of intraperitoneally transplantated human ovarian carcinoma model with immune reconstruction in severe combined immunodeficient mice

Objective To develop an intraperitoneally transplantated human ovarian carcinoma model in humanized severe combined immunodeficient (SCID) mice. Methods Twelve CB17SCID mice were randomly divided into 4 groups: group A intraperineally injected with phosphate buffered saline, group B injected with human ovarian carcinoma cells SKOV3, group C injected with human peripheral blood lymphocyte (PBL) for immune reconstruction, and group D injected with PBL and SKOV3 cells. The behaviors of mice, tumor growth and morphology, human IgG in peripheral blood, cancer antigen 125 (CA125) immunohistochemical staining, tumor infiltrating lymphocyte (TIL), and status of graftversus host disease (GVHD) were detected. Results The survival period was >28 days in all groups. The ratio of successful tumor transplantation was 3/3 in groups B and D. The tumor was widespread in peritoneal cavity, mainly in diaphragm, liver, and mesentery, with bloody ascites. The number and size of tumor were less in the humanized group. CA125 expression was positive in primary transplanted tumor cells and SKOV3 cells. IgG was detected in humanized groups (C and D). The level of human IgG was significantly higher in group D than in group C ( P <0.05). TIL infiltration was remarkable in group injected with PBL and SKOV3 cells and failed to be found in group injected with SKOV3 cells. No GVHD was found in all groups. Conclusion An intraperitoneal tranplanted human ovarian carcinoma model has been established in humanized SCID mice that simulates the biological behavior of human ovarian carcinoma disseminating intraperitoneally in patients with immune function and may function as an ideal animal model for preclinical research of ovarian carcinoma treatment.