本文選題：小鼠模型 + 阿糖胞苷　； 參考：《蘇州大學(xué)》2013年碩士論文

【摘要】：背景摘要一直以來(lái)，，AML的預(yù)后在臨床上都是一個(gè)很大的挑戰(zhàn)，大約60%到80%的病人是死于疾病的復(fù)發(fā)。雖然關(guān)于白血病的化療療效有大量的研究在開(kāi)展，但是導(dǎo)致該疾病預(yù)后很差的關(guān)鍵因素仍然不清楚，有待在體內(nèi)進(jìn)一步研究。 目的建立一個(gè)非免疫缺陷型AML小鼠模型，并建立一個(gè)有效的以Ara-C為基礎(chǔ)的AML體內(nèi)治療方案；同時(shí)運(yùn)用移植的AML小鼠模型來(lái)研究是否腫瘤細(xì)胞的數(shù)量及細(xì)胞固有對(duì)Ara-C（阿糖胞苷）的敏感性能夠影響AML的化療療效，并且在基因水平探究細(xì)胞敏感性影響化療效果的可能原因。 方法通過(guò)尾靜脈將BXH-2髓系白血病細(xì)胞注射到B6C3F1（C57BL/6雌性×C3H/HeJ雄性）小鼠體內(nèi)，7天后，通過(guò)腹腔注射Ara-C的方法來(lái)治療小鼠，對(duì)照組小鼠注射PBS（生理鹽水），連續(xù)注射10天。之后停止注射5天，讓藥物充分發(fā)揮藥效，接下來(lái)是另外一個(gè)10天的治療。第二階段治療結(jié)束后觀察小鼠狀態(tài)，于臨死前進(jìn)行解剖，運(yùn)用生存曲線來(lái)計(jì)算小鼠的存活率。 結(jié)果數(shù)據(jù)顯示：1）所有的B6C3F1小鼠在注射了BXH-2髓系白血病細(xì)胞后都能夠顯示出和急性髓系白血病相似的臨床癥狀，即成功建立了AML非免疫缺陷型小鼠模型；2）成功建立了一個(gè)有效的以Ara-C為基礎(chǔ)的治療方案，該方案包括2個(gè)間隔的10天治療階段，相比于給予PBS組別，經(jīng)過(guò)Ara-C治療小鼠的生存時(shí)間明顯延長(zhǎng)；3）注射較少白血病細(xì)胞或注射較敏感的白血病細(xì)胞的小鼠生存時(shí)間要明顯長(zhǎng)于對(duì)應(yīng)的組別；4）通過(guò)Microarray分析顯示：相比于敏感性白血病細(xì)胞基因組表達(dá)水平，耐藥性白血病細(xì)胞基因組變化超過(guò)5.5倍的共計(jì)約578個(gè)基因，其中366個(gè)基因表達(dá)水平上調(diào)，有212個(gè)基因表達(dá)水平發(fā)生下調(diào)。 結(jié)論研究結(jié)果顯示B6C3F1小鼠能夠順利的建立非免疫缺陷型AML模型；細(xì)胞固有因素、包括基因表達(dá)水平的差異可能在很大程度上決定著AML的治療效果。
[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.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類(lèi)號(hào)】：R-332;R733.71

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