热消融联合消融灶周边注射CpG ODN抑制小鼠肝癌生长的研究

摘要

目的 探讨热消融联合消融灶周边注射CpG ODN治疗对小鼠肝癌的影响及继发免疫效应的抗肿瘤效果.方法 建立Hepa1-6小鼠皮下肝癌动物模型32只,随机分为热消融治疗组、热消融联合CpG ODN治疗组、CpG ODN治疗组和对照组,每组8只.每组各6只接种肿瘤细胞后第7天、第14天给予治疗,测量小鼠肿瘤体积,观察荷瘤小鼠存活率及消融灶内淋巴细胞和HSP70变化,另8只第7天给予治疗,30 d后对侧接种等量肿瘤细胞,1个月后处死,观察小鼠生存状况及对侧肿瘤生长情况.结果 (1)各实验组小鼠观察期内死亡率均低于对照组(P＜0.05),各实验组对侧均无肿瘤生长,对照组再接种肿瘤生长率为100%(3/3),两者相比差异有统计学意义(P＜0.05);(2)各实验组小鼠与对照组相比,肿瘤体积显著缩小(P＜0.05),联合治疗组肿瘤缩小更显著;(3)各实验组较对照组有较多淋巴细胞浸润(P＜0.05),联合治疗组数量最多;(4)各实验组与对照组相比有更多HSP70表达(P＜0.05),联合治疗组HSP70表达最多,与其余实验组相比差异有统计学意义(P＜0.05).结论 CpG ODN对荷瘤小鼠具有明显的免疫增强作用,CpG ODN联合热消融治疗小鼠肝癌有效,且能减少复发.%Objective To investigate the therapeutic effect of thermal ablation combined with CpG ODN on the treatment of liver cancer in mice. Methods After the subcutaneous tumor model( Hepa1 -6 )was established in mice,32 mice were randomly divided int0 4 groups( n =8 ). Except the control group,tumor cells were injected into 6 mice in each group at the 7th day and the 14th day. 30 days after the first therapy, their tumor volumes, survival rate and the growth status were recorded. The remainder of the mice were injected equal amount of tumor cells on an opposite side 30 days later, their tumor volume, survival rate and the growth status were recorded. Results ( 1 )The mortality rate of experimental groups were lower than that of control group( P ＜ 0. 05 ), no tumor existed in experimental groups.( 2 )Compared with control group , tumor volume in each experimental group were reduced significantly( P ＜ 0. 05 ) , but in combination therapy group, tumor volume reduced most significantly. ( 3 )CD4+ cells and CD8+ numbers in each experimental group were significantly higher than those of control group( P ＜ 0. 05 ),in combination therapy group,which were much more than those of other groups. ( 4 )Compared with control group, the labeling index of HSP70 in each experimental group increased significantly( P ＜ 0. 05 ) ,in combination therapy group , which were more significant than those in others groups( P ＜0. 05 ). Conclusion CpG ODN can strengthen the immunity of Hepa1 -6 mice , CpG ODN combined with thermal ablation can effective cure rice liver, and reduce recurrence effectively.