论文部分内容阅读
目的 探讨反义寡核苷酸 (ODNs)对丙型肝炎病毒 (HCV)转染胆管癌细胞中HCV的抑制作用。方法 通过半定量逆转录 聚合酶链反应 (RT PCR)检测HCVmRNA表达的变化 ,观察不同浓度 (0~ 6 .0 μmol/L)的HCV核心区ODNs对体外丙肝病毒感染胆管癌细胞 (QBC939)的抑制作用 ;同时以裸鼠为研究对象进一步观察ODNs对HCV的体内抑制作用。结果 ODNs可有效地进入靶细胞在体外与HCV核心基因杂交结合 ,使HCVmRNA的表达明显降低 ,终浓度为 6μmol/L的ODNs作用下无HCVmRNA表达。动物实验观察ODNs组在裸鼠中的瘤体平均直径小于对照组、PBK HCVC转染组 (P <0 .0 1 ) ,成瘤率 2 5 % (5/ 2 0 )低于PBK HCVC转染组 65 % (1 3/2 0 ) (P <0 .0 5) ,成瘤时间 1 5 .3d较对照组 1 2 .0d、PBK HCVC转染组 1 0 .1d延迟 (P <0 .0 1 )。结论 反义寡核苷酸不失为治疗丙肝病毒感染胆管癌新的途径
Objective To investigate the inhibitory effects of antisense oligonucleotides (ODNs) on HCV in Hepatitis B virus (HCV) transfected cholangiocarcinoma cells. Methods The changes of HCV mRNA expression were detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and the effect of ODNs of different concentrations (0-6.0 μmol / L) on the in vitro in vitro susceptibility of hepatitis C virus-infected cholangiocarcinoma cells Inhibitory effect; At the same time to nude mice as the object to further observe the ODNs in vivo inhibition of HCV. Results ODNs could efficiently enter target cells and hybridize with HCV core gene in vitro, so that the expression of HCV mRNA was significantly reduced. No ODNs of 6 μmol / L were expressed on HCV mRNA. Animal experiments observed ODNs group in nude mice tumor diameter smaller than the control group, PBK HCVC transfection group (P <0.01), tumor formation rate of 25% (5/20) lower than PBK HCVC transfection (P <0.05). The tumorigenic time was 15.3d compared with that of the control group at 12.0d, and the PBK HCVC transfected group was delayed by 10.1d (P <0. 0 5) 1 ). Conclusion Antisense oligonucleotides are a new way to treat hepatitis C virus infection in cholangiocarcinoma