Objective The aim of our study is to develop a human hepatocellular carcinoma xenograft model in pigs and explore whether human cells could survive in pig liver，and to provide foundation information for clinical therapy of cancer in drug trials. Methods HepG2-Puro-GFP cells were injected into the Bama miniature pig’s liver which has been implemented partial hepatectomy by laparoscopic surgical procedures. Experiment were conducted in three groups（G0，G1 and G2）. Bama miniature pigs in G0 were injected with saline after implemented partial hepatectomy（sham）. Pigs in G1 were injected with human HepG2-Puro-GFP cells after implemented partial hepatectomy. Finally，pigs in G2 were also injected with human HeG2-Puro-GFP cells after implemented partial hepatectomy，and fed with immunosuppressant after surgery. The peripheral blood of each group was collected according to a certain time interval to detect the levels of alanine aminotransferase（ALT），aspartate transaminase （AST）and human alpha-feto protein（AFP）. Bama miniature pig’s liver tissues were harvested for hematoxylineosin（HE）staining to observe the morphologic features of the pig liver，and the survival of HepG2-Puro-GFcells were detected by immunohistochemistry staining. Results Levels of ALT and AST in each group restored to preoperative levels about 2 weeks after surgery. GFP-immunohistochemistry staining demonstrated that human HepG2 cells could exist in the G1 and G2 pig livers. Enzyme linked immunosorbent assay（ELISA）test indicated the expression of human AFP in the peripheral blood of the pigs in G1 and G2 groups. G2 group compared with G1 group, the difference was statistically significant〔AFP（μg/L）：39.54±20.30 vs. 13.77±7.52，P ＜ 0.05〕. HE staining showed the part of pigs had pathological changes in the liver，which included inflammatory cell infiltration and hepatocyte necrosis. Conclusion The pig model of human hepatocellular carcinoma can be achieved by orthotopic implantation of human hepatoma cells after partial hepatectomy. Immunosuppressant could prolong cells' survival time and survival efficiency.

目的 建立人肝癌巴马小型猪异种移植模型，探索人肝癌细胞是否能在猪的肝脏中存活， 为建立人肿瘤细胞异种移植的大动物模型和临床肿瘤治疗、药物试验等研究奠定实验基础。方法 将表达 GFP 的人肝癌细胞通过腹腔镜手术注入 15 只肝部分切除的巴马小型猪的肝实质中。实验分为 3 组（G0 组、 G1 组和 G2 组）。G0 组为对照组，巴马小型猪肝脏实行肝部分切除术后注射生理盐水 ；G1 组巴马小型猪实 施肝部分切除术后注射人肝癌细胞 ；G2 组巴马小型猪实施肝部分切除术后注射人肝癌细胞，术后 12 小时 饲喂免疫抑制剂。定期采集各组实验动物的外周血，检测实验动物天冬氨酸转氨酶（AST）和丙氨酸转氨酶 （ALT）的变化，检测血清中是否存在人类甲胎蛋白（AFP）。对巴马小型猪的肝脏进行取材，苏木素-伊红（HE） 染色后镜下观察猪肝组织病理学特征。对实验组进行绿色荧光蛋白（GFP）免疫组织化学染色，检测组织 中是否有人肝癌细胞的嵌合。结果 各组巴马小型猪的 AST 和 ALT 指标在术后 14 天恢复到术前水平。GFP 免 疫组织化学结果显示在 G1 组和 G2 组巴马小型猪的肝脏中均能检测到人肝癌细胞。酶联免疫吸附试验（ELISA） 检测结果显示在实验组的外周血中可以检测到人 AFP 的表达 , 且 G2 组与 G1 组相比，差异具有统计学意义 〔AFP（μg/L）：39.54±20.30 比 13.77±7.52，P ＜ 0.05〕。HE 染色结果显示 G1 组肝组织出现淋巴细胞浸 润和肝细胞坏死。结论 通过猪肝原位移植人肝癌细胞的方法可以建立人肝癌巴马小型猪异种移植模型。 免疫抑制剂能促进移植的细胞存活。