Aptamer-siRNA核酸复合物对人慢性粒细胞白血病(CML)小鼠模型凋亡信号转导的影响  

Influence of Aptamer-si RNA Nucleic Acid Compands on the Apoptosis Signal Pathways in Chronic Myelogenous Leukemia Mouse Model

作　　者：王保全[1] 孟涛[2] 瞿静[1] 李卫华[1] 郭建阔[1] 申智慧 赵清辉[4] 庞晓斌[4] 

机构地区：[1]河南大学淮河医院,开封475004 [2]河南大学淮河临床学院,开封475001 [3]郑州大学附属肿瘤医院,郑州450009 [4]河南大学药学院,开封475001

出　　处：《基因组学与应用生物学》2016年第10期2555-2560,共6页Genomics and Applied Biology

基　　金：河南省卫生厅科技计划项目(201404032);河南省卫生厅项目(201404031)共同资助

摘　　要：SELEX技术筛选人慢性粒细胞白血病(CML)核酸适配子,合成aptamer-si RNA核酸复合物,观察aptamer-si RNA核酸复合物干预NOD/SCID小鼠慢性粒细胞白血病(CML)bcr-abl融合基因及P210、P53、TNF-α、bcl-xl相关因子表达水平。将K562细胞接种于全身照射后的裸鼠,待皮下成瘤后取出瘤块,制备成瘤细胞混悬液,再尾静脉接种于NOD/SCID小鼠,实验成功建立了全身播散型白血病模型,对实验小鼠行随机分组,以RT-PCR法检测aptamer-si RNA核酸复合物治疗小鼠体内bcr-abl融合基因表达水平,ELASA法检测小鼠P210、P53、TNF-α、bcl-xl表达水平。实验结果表明:Aptamer-si RNA核酸复合物可显著降低模型小鼠体内融合基因bcr-abl及融合蛋白P210表达水平,能提升P53表达,抑制TNF-α、bcl-xl过度表达,其抑制效果与aptamer-si RNA核酸复合物浓度有一定的相关性。aptamer-si RNA核酸复合物通过干预CMLbcr-abl融合基因及其表达的融合蛋白P210,影响细胞信号传导通路途径,有效阻断了CML传变的进展,揭示了aptamer-si RNA核酸复合物干预CML疾病的微观机理。To screen the nucleic acid aptamer of chronic myelogenous leukemia （CML） by SELEX technology and to synthesis the aptamer-siRNA nucleic acid compands, the intervention on bcr-abl fusion gene and P210, P53, TNF-α, bcr-abl gene expression levels were observed in NOD/SCID mice model of chronic myelogenous leukemia （CML）. Nude Mice exposed to total body irradiation were inoculated subcutaneously with K562 Cells. Then, the local K562 Cells tumor was taken out and the tumor tissues were selected for preparing single cell suspension, which was inoculated into irradiated NOD/SCID mise view vein vaccination. The results showed that the CML model was established successfully. The mice of mice model were randomely divided into 4 groups, bcr/abl fusion gene expression levels in mice was detected by RT-PCR method after the aptamer-siRNA nucleic acid compand treatment. The expression level of P210, P53, TNF-α, bcl-xl were detected by ELASA method. The aptmer-siRNA nucleic acid compands had good inhibitory role in chronic myelogenous leukemia （CML） cells transmutation, which effectively suppressed the bcr-abl fusion gene expression and inhibit P210, TNF-α, bcl-xl, but raised the P53 expression, the effect of inhibition was related to aptamer-siRNA nucleic acid compand concentration. The aptamer-siRNA nucleic acid compands had a good role in inhibiting the chronic myelogenous leukemia （CML） cells transmutation by influencing the bcr/abl fusion gene expression and signal transduction mechansim.

关 键 词：aptamer-siRNA核酸复合物 慢性粒细胞白血病 凋亡信号传导 表达研究 

分 类 号：R733.72[医药卫生—肿瘤] R-332[医药卫生—临床医学]