为了筛选抗乙型肝炎（HBV）反义寡核苷酸药物，根据HBV基因组序列择S基因起始区、SPⅡ帽子区、前核心基因起始区、核心起始区、包装信号起始区等5个基因靶位点，设计并合成硫代反义寡核苷酸（S－asODN），以HePG22215细胞为研究对象，利用ELIAS法、MTT比色法、电子显微镜观察等手段，观察上述s－asODN对HePG22215细胞HBsAg和HBeAg表达以及对细胞的杀伤作用和细胞形态、超微结构的影响，结果显示s－asODN能显著抑制HBsAg和HBeAg的表达，s－asODN抗HBV具有序列特异性、剂量相关性、抗核酸酶性、联合用药协同性。 In order to screen anti-HBV anti-sense oligonucleotide drugs, select the S gene start region, SP II hat region, pre-core gene start region, core start region, packaging signal start region, etc. according to the HBV genome sequence (S-asODN) was designed and synthesized. HepG22215 cells were used as research objects. The expression of s-asODN was detected by ELIAS, MTT colorimetric and electron microscopy. asODN on HepG22215 cells HBsAg and HBeAg expression and cytotoxicity and cell morphology, ultrastructure, the results showed that s-asODN can significantly inhibit the expression of HBsAg and HBeAg, s-asODN anti-HBV with sequence-specific, dose-dependent Sexual, anti-nuclease, synergistic combination therapy.