【摘要】 目的　寻找抗HBV最佳反义寡核苷酸区段。方法　合成4种互补于HBV不同区段的反义硫代寡核苷酸(asON),加入HBV基因转染的肝癌细胞模型HepG22.2.15,以ELISA法测定HBsAg、HBeAg含量。结果　互补于preS2翻译起始区的asON(序列Ⅰ)抗HBV基因表达作用最强(P<0.02),对HBsAg、HBeAg的最高表达抑制率分别为66%和91%,针对增强子Ⅱ(ENⅡ)的序列Ⅲ也有较强的抑制作用(52%、56%)。asON抗HBV作用具有明显时相性,其抑制作用随时间延长而有反跳,且针对增强子Ⅱ的反义序列Ⅲ和针对S基因起始区的反义序列Ⅱ的抑制作用规律相似,并在时相上与序列Ⅰ互补。结论　4种asON中,序列Ⅰ抗HBV基因表达作用最强,而且序列Ⅰ与Ⅲ或Ⅱ配伍有望成为理想的抗HBV基因药物。更多还原

【Abstract】 Objective To explore an effective anti HBV oligodeoxynucleotide. Methods Four antisense phosphorothioate oligodeoxynucleotides (asON), complementary to different sites of HBV, were synthesized and assayed for their anti HBV activity in HepG 22.2.15 cells with ELISA. Results The oligomer directed against the initiator of pre S2 (No.Ⅰ) was most effective, with an inhibitory rate of 66% on HBsAg and 91% on HBeAg (P<0.02). The decrease in virus production was time dependent. The asON, complementary to enhancer Ⅱ (No.Ⅲ), or asON directed against initiator of S gene (No.Ⅱ) together with asON (No.Ⅰ) had an co inhibition effect on HBV gene expression. Conclusion asON directed against initiator of S gene had a strong inhibition effect on HBV and asON (No.Ⅰ), or asON (No.Ⅰ) together with asON( No.Ⅲ /Ⅱ) had a therapeutic potential in the treatment of patients infected with HBV.更多还原