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目的:探讨新设计CpG寡聚脱氧核苷酸(ODN)在小鼠体内的抗肿瘤作用及其对荷瘤小鼠免疫功能的影响。方法:建立C57BL/6小鼠腹腔、皮下荷黑素瘤肿瘤模型,腹腔注射CpGODN,观察荷瘤鼠生存时间、肿瘤生长曲线,计算抑瘤率。用酶联免疫吸附试验(ELISA)检测小鼠血清中白细胞介素(IL)12和免疫球蛋白E(IgE)含量;3H-TDR掺入法检测脾脏B细胞、T细胞增殖活性;51Cr释放法检测NK细胞杀伤活性;中性红法检测腹腔巨噬细胞吞噬功能。结果:CpG10,CpG11能明显延长腹腔接种肿瘤小鼠的生存时间,与阳性对照CPG1826相比P<0.01;二者平均抑瘤率(皮下荷瘤鼠)分别为(55.2±2.3)%与(40.7±1.7)%,显著高于CpG1826[抑瘤率(17.8±7.6)%](P<0.05,P<0.01)。CpG10/CpG11可促使荷瘤小鼠血清IL-12含量显著升高(P<0.01),IgE含量显著下降(P<0.01);明显刺激B细胞、T细胞增殖能力以及NK细胞的杀伤活性(P<0.01),对腹腔巨噬细胞的吞噬功能有显著提高(P<0.01)。CpGl0免疫增强活性较CPGl826更强(P<0.05)。结论:CpGODN能激活荷瘤鼠抗肿瘤免疫反应,从而抑制小鼠黑素瘤的生长,新结构寡核苷酸的CpG10呈现优于阳性对照的良好抗肿瘤免疫效应。
Objective: To investigate the antitumor effect of newly designed CpG oligodeoxynucleotide (ODN) in mice and its effect on immune function of tumor-bearing mice. Methods: C57BL / 6 mice were intraperitoneally and subcutaneously injected with melanoma tumor model. CpG ODN was injected intraperitoneally. The survival time and growth curve of tumor-bearing mice were observed. The tumor inhibition rate was calculated. Serum levels of interleukin (IL) 12 and IgE were detected by enzyme linked immunosorbent assay (ELISA); 3H-TDR incorporation assay was used to detect the proliferation of B cells and T cells in spleen; 51Cr release assay Detection of NK cell killing activity; Neutral red method to detect phagocytic function of peritoneal macrophages. Results: CpG10 and CpG11 could significantly prolong the survival time of mice with intraperitoneal inoculation compared with that of CPG1826 (P <0.01). The average tumor inhibition rates of the two groups were 55.2 ± 2.3% and 40.7% ± 1.7%), which was significantly higher than that of CpG1826 (17.8 ± 7.6%) (P <0.05, P <0.01). CpG10 / CpG11 could promote the level of IL-12 in serum of tumor-bearing mice significantly (P <0.01) and decrease the content of IgE (P <0.01), and significantly stimulate the proliferation of B cells, T cells and NK cells <0.01), phagocytosis of peritoneal macrophages was significantly increased (P <0.01). The immunostimulant activity of CpG10 was stronger than that of CPG1826 (P <0.05). CONCLUSION: CpG ODN can activate the anti-tumor immune response of tumor-bearing mice and inhibit the growth of mouse melanoma. CpG10 of the new structural oligonucleotide shows good anti-tumor immune effect over the positive control.