【摘要】 目的:探讨人白细胞介素(interleukin,IL)-12重组质粒对荷瘤小鼠的基因治疗作用,并进行初步的安全性评价。方法:建立肉瘤细胞(S-180)荷瘤小鼠模型,随机分为3组,每组10只,分别于注射瘤细胞后的第4、7、10、14和17天给予人IL-12重组质粒(pcDNA6-p70,100μg/只)、环磷酰胺(40mg/kg)及生理盐水(100μL/只)瘤体内注射。观察小鼠的存活时间;于致瘤后第21天处死小鼠,测肿瘤大小及质量,计算脾和胸腺指数;乳酸脱氢酶法检测NK杀伤活性;MTT法检测脾淋巴细胞增殖反应;ELISA法检测小鼠血清IFN-γ水平。对pcDNA6-p70小鼠体内运用进行初步的安全性评价。结果:与生理盐水组相比,pcDNA6-p70瘤体内注射可显著延长荷瘤小鼠存活时间,P=0.03;缩小肿瘤体积,抑瘤率为30%,生理盐水组为0;增加脾(P=0.04)及胸腺(P=0.019)指数,增强其NK活性(P=0.001)及淋巴细胞增生反应(P=0.000),提高荷瘤血清IFN-γ水平(P=0.000)。安全性检测结果显示,pcDNA6p70在小鼠体内应用无明显毒副作用,P=0.58。结论:人IL-12重组质粒可通过增强机体的细胞免疫功能发挥对肿瘤的基因治疗作用。更多还原

【Abstract】 OBJECTIVE:To investigate the genetic treatment of a recombinant plasmid coding human interleukin-12 (rIL-12, pcDNA6-p70) on transplanted tumor model of mice. METHODS: Tumor bearing mice were prepared by translanting sarcoma 180 cells (S-180)and divided into 3 groups at random (10 cases in each group), and pcDNA6-P70 (one mouse with 100 μg), cyclophosphamide(40 mg/kg) and sodium chloride (100 μL each/mouse) were directly injected into the tumor respectively at 4,7,10,14,17 days after the S-180 planted. Then the mice were sacrificed at the 21th day, their survival period, tumor volume of the mice was inspected, the activity of NK cells and lymphocyte proliferation from the spleen cells were measured and the production of IFN-γ of spleen lymphocyte was investigated. The security of pcDNA6-p70 was detected. RESULTS: Compared with the sodium chloride group,pcDNA6-p70 prolonged the life of tumor bearing mouse, P=0.03, belittled tumor, and the ratio to restrain the tumor was 30%, but it in the sodium chloride group was 0. pcDNA6-p70 enhanced the proliferative responses of spleen cells, increased the activity of NK cells and the serum level of IFN-γ,P was 0.04, 0.019, 0.001, 0.000 and 0.000, and it had better safety effects, P=0.58. CONCLUSION: rIL-12 plasmid could exert genetic therapy in tumor model by triggering the anti-tumor cellular immunity.更多还原