【摘要】 目的 研究反义核酸的抗病毒作用。方法 设计合成了针对鸭乙型肝炎病毒(DHBV)前S(PreS)基因区第951-968位核苷酸的硫代反义寡脱氧核苷酸(AS-ODN)，以20μg/g体重/日剂量对3只腹腔感染DHBV5.2毒株后，血清DHBsAg及DHBV DNA阳性鸭连续静脉注射10天，同时以等体积生理盐水注射另3只感染鸭作为对照。结果 对照鸭注射生理盐水后，血清DHBsAg及DHBV DNA阳性未见明显改变，肝组织DNA Southern杂交在3.0与2.3kb左右杂交信号明显。注射AS-ODN鸭在10天后，2/3鸭血清DHBsAg及DHBV DNA量显著降低，3/3鸭肝组织中3.0kb左右的杂交信号显著减弱，2.3kb左右未见杂交信号。结论 说明该段AS-ODN在鸭体内能部分抑制DHBV的复制与抗原表达。

Abstract To study the antiviral effect of antisense oligodoxynucleotide (AS-ODN), AS-ODN phosphotioates targeted to DHBV Pre-S region (951-968nt) (5'-TATCTCCTCCATTGTTTG-3') was synthesized. Two day-old ducklings were infected i.p. with 150μl of DHBV (3×10⁸ copies/ml DHBV). After 12 dyas, 6 DHBsAg and DHBV DNA positive ducks were divided into two groups. In treated group, each duck was injected i.v. AS-ODN 20μg/gram weight/day for 10 dyas successively, while in the control group, each duck received the same volume of normal saline for 10 days. Sera from ducks prior to treatment and treated after 6, 10 days were collected, and after 10 days ducks were sacrificed and livers were examined. DHBsAg was significantly decreased in all three treated ducks after 10 days of AS-ODN treatment. One of these ducks showed decreased DHBsAg even 6 days after treatment. Two out of three treated ducks showed decreased serum DHBV DNA, while one remained unchanged. In contrast, none of the control group showed decreased DHBsAg and DHBV DNA did not change. By Southern blot, DHBV DNA in the liver significantly decreased in 2/3 of the treated ducks and decreased in the other duck. In all control ducks, DHBV DNA remained strongly positive. Data indicated that AS-ODN targeting at Pre-S region could partly inhibit the replication of DHBV.

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