反义核酸抑制荷瘤裸鼠乙肝病毒基因表达

INHIBITION OF HEPATITIS B VIRAL GENE EXPRESSION BY ANTISENSE OLIGONU CLEOTIDES IN NUDE MICE BEARING 2.2.15 TUMOR

应用２．２．１５细胞（ＨＢＶ基因转染的ＨｅｐＧ２细胞株）转种裸鼠，建立荷瘤裸鼠ＨＢＶ动物模型。受种裸鼠皮下可迅速长出移植瘤并分泌ＨＢＶ多项标志物至外周血液中。应用互补于ＨＢＶｍＲＮＡＳＰⅡ增强子区的１５聚反义硫代寡核苷酸以２０μｇ／ｇ鼠体重剂量连续治疗１０ｄ，结果治疗组荷瘤裸鼠血清中ＨＢｓＡｇ、ＨＢｅＡｇ及ＨＢＶ－ＤＮＡ均受到明显抑制。证明该反义核酸在动物体内同样具有良好的抗病毒效应，为从基因水平研制新一代抗乙肝病毒药物奠定了基础。

cells (Hep G2 cell line transfected with HBV genome) were injected subcutaneously into athymic nude mice to establish animal model producing HBV markers. Transplanted tumor was grown up about 2 weeks after cells inoculation。 HBsAg and HBeAg as well as HBV DNA could be detected in the circulation of tumor bearing mice. Antisense phosphorothioate oligonucleotides which complementary to the cap site of SP Ⅱ promoter of HBV mRNA were injected by infiItration into or around the tumor with a daily dose of 20 μg per gram body weight. Treatment for a total of 10 days resulted In an effective inhibition of viral replication and gene expression in nude mice. These resuIts suggested a therapeutic potential for antisense oligomers in the treatment of patients who are chronically infected with HBV。