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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。
Objectives ① To explore a method for modeling non-Hodgkin’s lymphoma (NHL) animal models; ② to investigate the metabolic disorder of tryptophan involved in the induction of indoleamine 2,3 dioxygenase (IDO) and tryptophanyl tRNA synthetase (TTS) Correlation with NHL cell proliferation and NHL immune tolerance. Methods Inbred BALB / c mice were randomly divided into control group (n = 4), tumor group (n = 8) and treatment group (n = 8). Rat inoculated with NHL cell line A20 ) Animal model of NHL was established. The IDO inhibitor 1-methyltryptophan (1-MT) was injected into the tumor and tumor in vivo. The expression of TTS in tumor tissues and lymph nodes was detected by immunohistochemical SP method and Western blot. Results ① BALB / c mice were inoculated subcutaneously with A20 cells to establish animal models of lymphoma. The rate of tumor formation was high, the mortality of mice was low, accompanied by obvious lymph node and spleen metastasis. ② The expression of TTS in tumor tissues and metastatic lymph nodes was significantly increased by immunohistochemistry (P <0.05). ③Western blot results showed that compared with the normal control group, the TTS expression in the tumor tissue and the treated group was significantly increased (P <0.001). Compared with the tumor group, the TTS expression level in the treated group was significantly decreased (P <0.01). The expression of TTS in tumor metastasis lymph nodes had no change (P> 0.05). Conclusion Upregulation of TTS in low tryptophan microenvironment induced by IDO is one of the important mechanisms of tumor cells against IDO-induced tryptophan depletion and maintenance of their own metabolic processes. The regulation of 1-MT on tryptophan metabolic activity and expression level is expected to become a new direction for adjuvant treatment of malignant tumors.