摘要
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 antiviral effect of targeted antisense oligodeoxynucleotides (asODN) in HBV transgenic mice. Methods asODN phosphorothioated (5' -CATGCCCCAAAGCCAC-3') targeted to HBV pre-C/C region was synthesized. Gall5-PLL was used as drugs carrier which targeted asODN to mice liver. Twelve mice with positive serum HBsAg, HBV-DNA were divided into the Gall5-PLL- asODN-treated group or the control group randomly. In Gall5-PLL- asODN-treated group, each mouse was injected i.v. asODN 15μg/g weighty/day via tail vein for 12 days successively; while in the control group, each mouse received the same volume normal saline by the same way. Results In the Gall5-PLL- asODN-treated group, serum HBsAg decreased at the 6th day (P<0.05), and decreased significantly at the 12th day vs pretreatment (P<0.01). The serum HBV DNA of 4/6 mice became negative. Immunohistochemistry test showed lowerd HBsAg, HBcAg content in the liver. In contrast, the control group showed no apparent changes. Conclusions Gall5-PLL-asODN targeted to pre-C/C region could inhibit HBV replication and gene expression.
出处
《中华肝脏病杂志》
CAS
CSCD
2002年第4期283-286,共4页
Chinese Journal of Hepatology
基金
国家自然科学基金(39370648)
