应用急性髓系白血病小鼠模型，探究细胞固有因素对阿糖胞苷化疗效果的影响

发布时间：2018-06-17 00:21

本文选题：小鼠模型 + 阿糖胞苷　；参考：《苏州大学》2013年硕士论文

【摘要】：背景摘要一直以来，，AML的预后在临床上都是一个很大的挑战，大约60%到80%的病人是死于疾病的复发。虽然关于白血病的化疗疗效有大量的研究在开展，但是导致该疾病预后很差的关键因素仍然不清楚，有待在体内进一步研究。目的建立一个非免疫缺陷型AML小鼠模型，并建立一个有效的以Ara-C为基础的AML体内治疗方案；同时运用移植的AML小鼠模型来研究是否肿瘤细胞的数量及细胞固有对Ara-C（阿糖胞苷）的敏感性能够影响AML的化疗疗效，并且在基因水平探究细胞敏感性影响化疗效果的可能原因。方法通过尾静脉将BXH-2髓系白血病细胞注射到B6C3F1（C57BL/6雌性×C3H/HeJ雄性）小鼠体内，7天后，通过腹腔注射Ara-C的方法来治疗小鼠，对照组小鼠注射PBS（生理盐水），连续注射10天。之后停止注射5天，让药物充分发挥药效，接下来是另外一个10天的治疗。第二阶段治疗结束后观察小鼠状态，于临死前进行解剖，运用生存曲线来计算小鼠的存活率。结果数据显示：1）所有的B6C3F1小鼠在注射了BXH-2髓系白血病细胞后都能够显示出和急性髓系白血病相似的临床症状，即成功建立了AML非免疫缺陷型小鼠模型；2）成功建立了一个有效的以Ara-C为基础的治疗方案，该方案包括2个间隔的10天治疗阶段，相比于给予PBS组别，经过Ara-C治疗小鼠的生存时间明显延长；3）注射较少白血病细胞或注射较敏感的白血病细胞的小鼠生存时间要明显长于对应的组别；4）通过Microarray分析显示：相比于敏感性白血病细胞基因组表达水平，耐药性白血病细胞基因组变化超过5.5倍的共计约578个基因，其中366个基因表达水平上调，有212个基因表达水平发生下调。结论研究结果显示B6C3F1小鼠能够顺利的建立非免疫缺陷型AML模型；细胞固有因素、包括基因表达水平的差异可能在很大程度上决定着AML的治疗效果。
[Abstract]:Background the prognosis of AML has been a great challenge in clinical practice. About 60% to 80% of the patients died of recurrence of the disease. Although a large number of studies have been carried out on the chemotherapeutic efficacy of leukemia, the key factors contributing to the poor prognosis of the disease remain unclear and need to be further studied in vivo. Objective to establish a model of non-immunodeficient AML mice and to establish an effective in vivo treatment of AML based on Ara-C; At the same time, the transplanted AML mouse model was used to study whether the number of tumor cells and the inherent sensitivity of tumor cells to Ara-C- (cytarabine) could affect the chemotherapeutic efficacy of AML, and to explore the possible causes of cell sensitivity affecting chemotherapeutic effect at the gene level. Methods BXH-2 myeloid leukemia cells were injected into B6C3F1C57BL / 6 female 脳 C3H / HeJ mice by tail vein for 7 days. The mice were treated by intraperitoneal injection of Ara-C. The control mice were injected with PBSs (normal saline) for 10 days. The injection was then stopped for 5 days to give full effect to the drug, followed by another 10 days of treatment. At the end of the second stage, the state of the mice was observed and dissected before death. The survival curve was used to calculate the survival rate of the mice. Results the data showed that all B6C3F1 mice were able to show similar clinical symptoms to acute myeloid leukemia after BXH-2 myeloid leukemia cells were injected, that is to say, the AML non-immunodeficient mouse model was successfully established. 2) an effective Ara-C based treatment scheme was successfully established, which included two interval 10-day treatment stages, and the survival time of mice treated with Ara-C was significantly longer than that of PBS group. 3) the survival time of mice injected with fewer leukemic cells or more sensitive leukemic cells was significantly longer than that of the corresponding group 4. The results of microarray analysis showed that the genomic expression level of the cells was higher than that of the sensitive leukemic cells. There were 578 genes whose genome changes were more than 5.5 times, 366 of which were up-regulated and 212 genes were down-regulated. Conclusion the results showed that B6C3F1 mice could successfully establish non-immunodeficient AML model, and the difference of cellular intrinsic factors, including gene expression level, might determine the therapeutic effect of AML to a great extent.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R-332;R733.71

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