摘要
目的 在HCV 5′NCR转基因细胞模型HepG2.9706细胞建立成功的基础上，采用裸鼠异植瘤模型进行HCV特异性硫代反义寡核苷酸(HCV363、HCV279及HCV349)的体内活性评价。 方法 将HepG2.9706细胞接种于4～6周龄的雌性BALB/C裸鼠的侧腹皮下，动物随机分组，约1周后，采用腹腔注射途径，开始给药。 结果 针对HCV 5′NCR的硫代反义寡核苷酸HCV363、HCV279及HCV349对异植瘤细胞内HCV 5′NCR调控荧光素酶表达具有明显的序列特异性抑制作用，抑制率分别为80.4%、78.6%及47.9%。三个不同浓度的HCV363作用结果表明随着药物浓度的增加，HCV363对荧光素酶基因的表达抑制活性明显增强，最大抑制率可达82.7%。 结论 该研究提示反义寡核苷酸有可能成为HCV感染治疗的新途径。
Objective To evaluate the activity in vivo of 3 phosphorothioate antisense oligonucleotides, HCV363, HCV279 and HCV349 using nude mice xenograft models based on the establishment of HCV 5' NCR transgenic cellular model (HepG2.9706). Methods Female BALB/C nude mice, aged 4 to 6 weeks and weighing around 20g, were implanted s.c. with 100μl (106 cells) of the HepG2.9706 cells suspension in the lower-back region. In approximate 1 weeks, the animals were randomly grouped and intraperitoneally administrated the antisense drugs at 10 mg/kg body weight. Results HCV363, HCV279 and HCV349 had obvious sequence-specific inhibitory effects on luciferase expression controlled by HCV 5' NCR in xenograft cells with the inhibitory rates of 80.4%, 78.6% and 47.9%, respectively. The effects of three different concentrations (5, 10, 20 mg/kg body weight) of HCV363 indicated that HCV363 increased the inhibitory activities on luciferase expression following the concentration raise and its inhibitory rate was up to 82.7%. Conclusions This study suggests that antisense oligonucleotides may provide a novel therapeutic approach to the treatment of HCV infection. [
出处
《中华肝脏病杂志》
CAS
CSCD
2001年第5期285-287,共3页
Chinese Journal of Hepatology
基金
国家"863"课题(102-08-04-01)
军队9.5重点课题(96Z007)
