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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。
Objective To study the effect of direct injection of recombinant retrovirus packaging cell line carrying interleukin 2 (IL-2) and / or interleukin 12 (IL-12) gene on blood IL-2 and IL-12 in rat spleen induced hepatoma model NK cell activity. Methods The rats were randomly divided into normal saline control group, empty vector control group, IL-12 gene therapy group, IL-2 gene therapy group and IL-2 / IL-12 combined gene therapy group. Construction of retroviral vector carrying IL-2 and / or IL-12 gene. After oral administration of diethylnitrosamine to induce cancer, the packaging cells containing IL-2 and / or IL-12 genes are transfected into splenocytes. The concentrations of IL-2 and IL-12 in serum, NK cell activity, pathological changes and toxicity were compared. Results IL-2 and IL-12 levels were significantly increased after IL treatment. The combined genome expressed both IL-2 and IL-12 at a higher level than the single-gene therapy group. Pathology showed significantly increased lymphocytic infiltration in HCC tissues. The activity of NK cells in IL treatment group was significantly higher than that in control group (P <0.01). The combined genome was higher than the IL single gene (P <0,05). Serum IL reached its peak 3 days after treatment, and then gradually decreased. Conclusion The direct injection of retroviral packaging cell line carrying IL-2 and / or IL-12 gene into the spleen can obviously enhance the activity of NK cells. IL combined with gene therapy is superior to IL single gene.