【摘要】 目的　比较人工合成的反义硫代寡核苷酸 (asODN )和反义RNA真核表达质粒 (PCEP4-ac)在乙型肝炎(HBV)病毒转基因小鼠体内的抗病毒作用。　方法　设计合成针对HBV -pre -c/c基因的反义硫代寡核苷酸 5‘ -CAT GCCCCAAAGCCAC -3’。构建HBV -c区反义RNA真核表达质粒 (PCEP4-ac) ,并以半乳糖 -多聚赖氨酸 (Gal15 -PLL)作肝靶向载体。将 2 0只HBV转基因小鼠分为反义寡核苷酸、反义RNA真核质粒表达、生理盐水组。靶向反义硫代寡核苷酸以每只体重 15 0ug剂量 ,反义RNA真核质粒每只 10 0ug剂量 ,尾静脉注射给药 ,对照组用同样体积生理盐水同样方法给药。　结果　注射asODN和PCEP4-aC后 7d血清HBsAg已有所下降 (P <0 .0 5 ) ;14d时显著下降 (P <0 .0 1) ,且血清HBV -DNA转阴率分别为 66.7% ( 4 /6)和 62 .5 % ( 5 /8) ,而生理盐水组无明显变化。　结论　反义硫代寡核苷酸和反义RNA真核表达质粒均能在乙肝转基因小鼠体内抑制HBV复制和表达 ,且两者在抑制作用上无明显差异性。更多还原

【Abstract】 Objective To investigate the antiviral effect of targeted antisense oligodeoxynucleotides (asODN) and targeted antisense RNA (pCEP 4-aC) 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. PCEP 4-aC. was incubated with galactosylated poly-L-Lysine(Gal-PLL) to produce the targeted Gal-PLL-pCEP 4-aC. Twenty mice whose HBV-DNA was positive were divided into the Gall5-PLL-asODN-treated group, the Gal-PLL-PCEP 4-aC-treated group and the control group randomly. In the Gall5-PLL-asODC and the Gal-PLL-PCEP 4-aC-treated group,each mouse was injected i.v. asODN 150 μg/g or Gal-PLL- pCEP 4-aC 100 μg/g weight/day via tail vein. While in the control group, each mouse received the same volume normal saline in the same way. Result In the Gall5-PLL-asODN and the Gal-PLL-PCEP 4-aC-treated group, serum HBsAg decreased at the 7th day (P<0.05), and decreased significantly at the 14th day vs pretreatment (P<0.01). The serum HBV DNA of 4/6 mice in the Gall5-PLL-asODN and 5/8 mice in the Gal-PLL-PCEP 4-aC-treated group became negative. In contrast, the control group showed no apparent changes. Conclusions Gall5-PLL-asODN targeted to pre-c/c region and the antisense RNA which targeted to the liver could inhibit HBV replication and gene expression, and no significant difference was found between the two treated groups.更多还原