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目的 探讨靶向反义硫代寡脱氧核苷酸（asODN）在乙型肝炎（HBV）病毒转基因小鼠体内抗病毒疗效。方法 设计合成针对HBV pre-C/C基因的反义硫代寡脱氧核苷酸:5＇-CATGCCCCAAAGCCAC-3＇,并以半乳糖-多聚赖氨酸（Gal15-PLL）作肝靶向载体。将12只血清HBsAg,HBV DNA阳性的转基因小鼠等分为 Gal15-PLL—asODN治疗组及生理盐水对照组。靶向反义硫代寡脱氧核苷酸以每天每克体重15μg剂量,尾静脉注射给药,共12d;对照组用同样体积生理盐水同样方法给药。结果 注射Gal15-PLL-asODN 6d后,血清HBsAg已有下降（P<0.05）;12d时显著下降（P<0.01）,且血清HBV DNA转阴率为66.7％（4/6）,肝组织免疫组织化学HBsAg、HBcAg阳性肝细胞数较对照组明显下降（P<0.05）;而生理盐水对照组无明显变化。结论 靶向反义硫代寡脱氧核苷酸在转基因小鼠体内能抑制HBV复制与抗原表达。
Objective To investigate the anti-virus effect of targeting antisense oligodeoxynucleotides (asODN) in hepatitis B virus (HBV) transgenic mice. Methods Antisense thio-oligodeoxynucleotide (5’-CATGCCCCAAAGCCAC-3 ’) against HBV pre-C / C gene was designed and synthesized. The target vector was Gal-PLL . 12 serum HBsAg and HBV DNA positive transgenic mice were equally divided into Gal15-PLL-asODN treatment group and saline control group. Targeted antisense thio oligodeoxynucleotides were administered intravenously at a dose of 15 μg / g body weight per day for 12 days. The control group was administered with the same volume of physiological saline. Results Serum HBsAg had been decreased (P <0.05) on the 6th day after injection of Gal15-PLL-asODN, significantly decreased on the 12th day (P <0.01), and the serum HBV DNA negative rate was 66.7% (4/6) Histochemical HBsAg, HBcAg positive hepatocytes decreased significantly compared with the control group (P <0.05), while the saline control group had no significant change. Conclusion Targeting antisense oligodeoxynucleotides can inhibit HBV replication and antigen expression in transgenic mice.