色氨酰tRNA合成酶对淋巴瘤小鼠细胞增殖的影响  

Influences of tryptophanyl-tRNA synthetase on cell proliferation of lymphoma in mice

作　　者：丁梅[1] 刘小倩[2] 高钧明[3] 王欣[1] 

机构地区：[1]山东大学附属省立医院血液科,济南250021 [2]烟台毓璜顶医院血液科,山东烟台264000 [3]山东省警官总医院,济南250002

出　　处：《山东大学学报（医学版）》2011年第12期48-51,57,共5页Journal of Shandong University:Health Sciences

基　　金：2010年山东省科技发展计划项目(2010GSF10250);2009年山东省自然科学基金项目(2009ZRB14176)2007年山东省自然科学基金项目(Y2007C053);2007年山东省科学技术发展计划项目(2007GG10002008)

摘　　要：目的①探索非霍奇金淋巴瘤(NHL)动物模型建模方法;②探讨吲哚胺2,3双加氧酶(IDO)及色氨酰tRNA合成酶(TTS)参与的色氨酸代谢紊乱与NHL细胞增殖及NHL免疫耐受的相关性。方法将近交系BALB/c小鼠随机分为对照组(4只)、肿瘤组(8只)和治疗组(8只),以鼠源性NHL细胞株A20皮下注射(5×106个/只)建立NHL动物模型,瘤旁及瘤内注射IDO抑制剂1-甲基色氨酸(1-MT),并采用免疫组化SP法和Western blot技术检测肿瘤组织和淋巴结中TTS的表达水平。结果①BALB/c小鼠皮下接种A20细胞建立淋巴瘤动物模型,成瘤率高,小鼠死亡率低,伴有明显的淋巴结和脾脏转移;②免疫组化示肿瘤组织及转移淋巴结TTS表达均升高(P<0.05);③Western blot结果显示,与正常对照比较,肿瘤组及治疗组小鼠肿瘤组织TTS表达明显升高(P<0.001);与肿瘤组相比,治疗组TTS表达水平显著下降(P<0.01),肿瘤转移淋巴结TTS表达无变化(P>0.05)。结论 IDO诱导的低色氨酸微环境中,TTS表达上调是肿瘤细胞对抗IDO诱导的色氨酸耗竭、维持自身代谢过程的重要机制之一。1-MT对色氨酸代谢活性及表达水平的调控有望成为辅助治疗恶性肿瘤的新方向。Objective ① To establish a BALB/c mouse lymphoma model and ②To investigate the correlation of trytophan metabolic imbalance and cell proliferation of non-Hodgkin lymphoma.Methods BALB/c mice were randomly divided into three groups,i.e.the control group,the lymphoma group and the IDO inhibitor（1-MT）group.A B lymphoma animal model was established by hypodermic injection of 5×106 A20 cells.Immunohistochemical streptavidin-peroxidase（SP）staining and Western blot were used to analyze expression of TTS among the three groups.Results ① The method of hypodermic injection of 5×106 A20 cells was easy to operate.The rate of tumor information was about 95%,and the metastasis to lymph node and spleen were definite.② Compared with the normal control,TTS showed a significantly higher expression in the tumor tissue in both the tumor group and the treatment group（P0.001）.Compared with the tumor group,TTS expression significantly decreased in the treatment group（P0.01）.No significant change of TTS expression was found in metastatic lymph nodes（P0.05）.Conclusions The up-regulation of TTS may be the protective mechnaism of cell proliferation in lymphoma to resist IDO-induced immunosuppression,which implies that 1-MT may provide a new pathway for clinical intervention.

关 键 词：淋巴瘤模型 动物 吲哚胺2 3双加氧酶 色氨酰tRNA合成酶 小鼠 近交BALBC 

分 类 号：R733.4[医药卫生—肿瘤]