大鼠诱发肝癌模型中脾内转染IL-2和IL-12基因激活NK细胞

目的研究大鼠诱发肝癌模型中脾内直接注射携带白介素2（IL-2）和（或）白介素12（IL-12）基因的逆转录病毒包装细胞株对血IL-2和IL-12,以及NK细胞活性的影响.方法大鼠随即分为生理盐水对照组、空载体对照组、IL-12基因治疗组、IL-2基因治疗组及IL-2/IL-12联合基因治疗组.构建携带IL-2和（或）IL-12基因的逆转录病毒载体.口服二乙基亚硝胺诱癌后,含IL-2和（或）IL-12基因的包装细胞转染脾细胞.比较大鼠血IL-2和IL-12浓度、NK细胞活性、病理变化和毒性反应.结果IL基因治疗后血IL-2和IL-12明显增加.联合基因组同时表达IL-2和IL-12,总水平高于单基因治疗组.病理示治疗后肝癌组织中淋巴细胞浸润明显增多.IL治疗组NK细胞活性较对照组显著增高（P＜0.01）.联合基因组较IL单基因增高（P＜0.05）.治疗后3 d血清IL达高峰,以后逐步下降.结论脾内直接注射携带IL-2和（或）IL-12基因的逆转录包装细胞株可明显增强NK细胞活性,IL联合基因治疗优于IL单基因.

Activation of NK cells by transfecting IL-2 and/or IL-12 gene into spleen in rats with induced liver cancer

Objective To study the intrasplenically injected retroviral packaging cells encoding IL-2 and IL-12 on serum IL and NK cell activity in rats with induced liver cancer. Methods The rats were randomized into the physiological saline control group, blank vector control group, IL-2 gene group, IL-12 gene group and hIL-2/mIL-12 fused gene group. The retroviral vectors encoding IL2 and/or IL-12 gene were constructed. After the liver cancer was induced in rats by oral administration of diethyl nitrosamine, packaging cells containing IL-2 and/or IL-12 gene were transfected into the splenic cells. The serum IL-2 and IL-12 levels, NK cell activity, liver pathology and toxic effect were investigated. Results The serum IL-2 and IL-12 were significantly increased. The IL-2 and IL-12 were expressed simultaneously in the combined gene group and the amount of IL was significantly higher compared with IL group alone. The pathological study showed that a number of lymphocytes infiltrated into the liver tissue in the IL-2/IL-12 group. Compared with the control, NK cell activity was markedly increased in IL group. IL-2/IL12 gene significantly activated NK cells compared with IL group alone. The peak activity of NK cell was detected on day 3 and then decreased step by step. Conclusions IL-2 and/or IL-12 gene directly injected into spleen can increase the NK cell activity. IL-2/ IL-12 gene is more efficient than IL gene alone for activating NK cells.