摘要
目的 观察白细胞介素２（ＩＬ－２）基因修饰的小鼠肝细胞经脾内移植后对肝脏免疫功能的影响以及对肝癌小鼠的治疗作用。方法将ＩＬ－２基因修饰的小鼠胚胎肝细胞ＢＮＬＣＬ．２做小鼠脾内移植（２×１０６／只）后２周，分离肝巨噬细胞（Ｋｕｐｆｆｅｒ细胞），检测其杀伤活性、肿瘤坏死因子（ＴＮＦ）和一氧化氮（ＮＯ）分泌水平及Ⅰａ抗原的表达，并观察其对Ｃ２６结肠癌肝转移小鼠的治疗作用。结果 实验组小鼠Ｋｕｐｆｆｅｒ细胞对不同靶细胞的杀伤活性显著增强，ＴＮＦ和ＮＯ分泌水平明显升高，Ⅰａ抗原的表达增加；经此方法治疗后，转移性肝癌小鼠的存活期显著延长。结论ＩＬ－２基因修饰的肝细胞脾内移植是肝癌基因治疗的有效途径，肝细胞脾内移植是肝脏靶向性基因治疗的途径之一。
Objective To investigate the effects of intrasplenically transplanted , IL-2 gene-modified hepato- cytes on the liver immune response and anti-tumor activity. Methods Murine fetal hepatocytes BNLCL. 2 were transfected with mIL-2 gene in vitro , and intrasplenically transplanted into syngeneic mice (2 ×10/mouse). After two weeks, the Kupffer cells were isolated and studied for cytotoxicity, TNFand NO production , and Ia expresson. The therapeutic effects on the mice with the metastatic liver car- cinoma were also observed . Results The Kupffer's cytotoxicity to L1210 . Yac- 1 , P815 and H22 targetcells , and their production of TNP and NO were greatly augmented , even when freshly prepared. Their Ia expression also increased . When treated with IL-2 gene-modified hepatocytes , the metastatic liver carcinoma-bearing mice survived for a longer time. Conclusions Intrasplenic transplantation of IL-gene-modified hepatocytes could effectively activate the liver immune response and exert potent thera- peutic effects on liver carcinoma-bearing host.
出处
《中华医学杂志》
CAS
CSCD
北大核心
1996年第9期646-649,共4页
National Medical Journal of China
基金
国家自然科学基金优秀中青年人才专项基金资助项目
