白细胞介素-15对小鼠胃癌的治疗作用

Interleukin 15 gene therapy mouse model of gastric carcinoma

目的建立小鼠胃癌模型，检测荷瘤状态对小鼠免疫细胞的影响，同时给予白细胞介素-15（IL-15）免疫基因治疗，以检测IL-15对胃癌的预防及治疗效果。方法采用多因素联合攻击法诱导小鼠胃癌，同时采用IL-15表达质粒载体进行免疫基因治疗。20周后取胃标本行病理学检查，并取血及脾细胞检测T细胞亚群及CD4＋CD25＋调节性T细胞（Treg）。同时进行自然杀伤（NK）细胞的细胞毒性试验，通过统计学方法分析结果。结果多因素联合攻击法诱导胃癌发生率为37．5％。诱癌组小鼠血清IL—15水平（9．20±2．92）ng／L明显降低（P〈0．05），且其脾NK细胞杀伤活性（216．91±117．80）U／L明显降低（P〈0．05）。诱癌组小鼠外周血Treg水平（8．07±6．62）％明显升高（P〈0．05），而对照组小鼠脾细胞Treg水平（4．40±3．34）％明显降低（P〈0．05）。各组小鼠之间外周血T细胞亚群变化差异无统计学意义（P〉0．05）。诱癌组小鼠脾细胞CD3＋T细胞水平（78．31±29．79）％明显升高（P〈0．05），而CD4＋T细胞（19．98±5．77）％及CD8＋T细胞水平（10．15±1．72）％明显降低（P〈0．05）。结论多因素联合攻击法为小鼠胃癌模型建立提供了良好的模型。小鼠荷瘤状态下免疫功能下降，通过IL—15免疫基因治疗可提高机免疫功能，起到抗肿瘤的效果。

Ohjeetive To establish mouse model of gastric carcinoma, and assess the effects of tumor-bearing state on the immune system and the therapeutic and preventive effects of interleukin 15 （ IL- 15 ） gene therapy. Methods Six-week-old male BALB/C mice were utilized to establish gastric cancer model through multiple carcinogens attaek. Gastric specimens were collected for pathologic study at the 20th week, and peripheral blood and splenoeytes were tested for T-cell subsets and Treg by flow eytometry. NK cell eytotoxieity was assessed to evaluate the effect of IL-15 gene therapy on gastric cancer, and data were analyzed statiseally. Results 37.5% of mice were successfully induced with gastric carcinoma on the week 20. Compared to the other two groups, IL-15 expression （9.20 ±2.92） ng/L and NK cell eytotoxicity （216.91 ± 117.80 ） U/L in cancer-induced group were significantly decreased （P 〈 0. 05 ）. Periphpearl blood Treg expression was significantly increased in the cancer-induce group （ 8.07 ± 6. 62 ） % , while spleenoeyte Treg expression was signifieantly decreased in the control group [ （4. 40 ± 3.34）%, P 〈 0. 05 ]. There was no significant difference in T cell subsets in the peripheral blood among the group （ P 〉 0. 05 ） , but in cancer-induced group the number of spleenoeyte CD3 ± T cells （78.31 ± 29.79）% was sig- nificantly increased （ P 〈 0. 05 ）, while that of CD4 ± T cells （ 19.98 ± 5.77 ） % and CD8 ± T cells （ 10. 15 ± 1.72） % was significantly decreased （ P 〈 0.05 ）. Conclusion Multiple carcinogens attack was an ideal way to establish mouse model of gastric carcinoma in mice. During tumor-bearing state, there was a significant deerease in immune function, and immunogene therapy with IL-15 plasmid vector can enhance immune function to achieve anti-tumor immune response.