双歧杆菌脂磷壁酸对化疗荷瘤小鼠免疫功能的影响  

Effect of lipoteichoic acid of Bifidobacterium on immune function of tumor-bearing mice with chemotherapy

作　　者：谢宁[1] 王跃[1] 刘明方[1] 李芙蓉[1] 王强[1] 郭斌[1] 

机构地区：[1]重庆医科大学临床检验诊断学教育部重点实验室医学检验系,重庆400016

出　　处：《中国微生态学杂志》2009年第4期327-331,共5页Chinese Journal of Microecology

摘　　要：目的探讨双歧杆菌脂磷壁酸对5-氟尿嘧啶(5-FU)化疗肝癌H22荷瘤小鼠免疫的影响及其作用机制。方法双歧杆菌脂磷壁酸处理5-FU化疗的H22荷瘤Balb/c小鼠,MTT法检测NK细胞和CTL细胞杀伤活性;采用流式细胞仪检测荷瘤小鼠脾细胞中T亚群比例;用RT-PCR和Western blot方法分别检测荷瘤小鼠肿瘤组织Foxp3和TIM-3 mRNA及蛋白的表达变化。结果荷瘤小鼠脾细胞中CD4+CD25+Treg比例高,并存在Foxp3和TIM-3 mRNA及蛋白的高表达,经双歧杆菌LTA和5-FU处理后CD4+CD25+Treg比例下降,Foxp3和TIM-3 mRNA及蛋白表达水平也均呈下调趋势,但5-FU单独处理后的荷瘤小鼠脾细胞中CD4+细胞比例也减少,NK细胞和CTL杀伤率均降低,而双歧杆菌LTA处理后CD4+细胞比例,NK细胞和CTL杀伤率却明显增加。二者联合处理也能增加CD4+细胞比例及NK细胞和CTL杀伤率。结论双歧杆菌脂磷壁酸联合5-FU可通过增强NK细胞和CTL杀伤能力,同时抑制TIM-3/TIM-3L途径,降低CD4+CD25+Treg的免疫抑制活性,增强机体细胞免疫来提高化疗抗肿瘤效果,减轻化疗副作用,增强宿主对化疗的耐受性,从而提高抗肿瘤作用。Objective To investigate the immunity effects and mechanism of lipoteichoie acid （LTA） of Bifidobacterium on the mice bearing inoculated H22 cells treated with 5-FU. Method Tumor-bearing mice were treated with 5-FU alone, LTA alone or LTA in combination with 5-FU. MTT assay was used to evaluate killing activity of NK cells and CTL cells. FCM was used to detect T subgroup ratio of spleen cells of tumor-bearing mice. Changes of mRNA and protein expression of Foxp3 and TIM-3 in tumor-bearing mice tumor tissue were detected by RT-PCR and Western blot. Result Spleen cells of tumor-bearing mice had high CD4^＋ CD25^＋ Tmg ratio and high mRNA and protein expression of Foxp3 and TIM-3. After treatment by LTA and 5-FU, the CD4^＋ CD25^＋ Tmg ratio degraded, with down regulation of mRNA and protein expression of Foxp3 and TIM-3. The CD4^＋T cells and the killing activity of NK and CTL cells decreaed after treated with 5- FU alone,while significantly increased by LTA treatment. LTA in combination with 5-FU could also enhance the ratio of CD4^＋ T cells and the killing activity of NK cells and CTL cells. Conclusion LTA of Bifidobacterium in combination with 5-FU could enhance anti-tumor effect and relieve side effect of chemotherapy by enhancing the killing capability of NK cells and CTL cells, inhibiting TIM-3/TIM-3 L pathway, cutting down immunosuppressive activity of CD4^＋~ CD25^＋ Tmg and enhancing cell-mediated immunity.

关 键 词：双歧杆菌 脂磷壁酸 5-氟尿嘧啶 免疫功能 

分 类 号：R730.5[医药卫生—肿瘤]