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目的 探讨半乳糖修饰的反义 RNA真核表达质粒在乙型肝炎病毒转基因小鼠体内的抗病毒作用。方法 以半乳糖多聚赖氨酸 (Gal- PL L )作肝靶向载体 ,将乙型肝炎病毒基因 C区的反义 RNA真核表达重组质粒 (p CEP4 -a C)制备为 Gal- PL L - p CEP4 - a C。将 2 4只血清 HBV DNA、HBs Ag阳性的小鼠 ,随机等分为 Gal- PL L - p CEP4 - a C治疗组、Gal- PL L - p CEP4对照组和生理盐水阴性对照组 ,于实验第 1天尾静脉分别注射 Gal- PL L - p CEP4 - a C、Gal- PL L - p CEP4(10 0μg/只 )和等体积的生理盐水 ,观察治疗前后血清 HBV DNA以及 HBs Ag变化。结果 Gal- PL L - p CEP4 - a C治疗组2 1天时血清 HBV- DNA转阴率 6 2 .5 % (5 / 8) ,且 7,14 ,2 1天时血清 HBs Ag明显降低 ;而 Gal- PL L - p CEP4组血清 HBVDNA转阴 1只 (1/ 8) ,生理盐水组 8只均未转阴 ,两组用药后血清中 HBs Ag与用药前比较差异性均不明显 (P>0 .0 5 )。结论 肝靶向反义 RNA能在乙肝基因小鼠体内抑制 HBV的复制和抗原表达
Objective To investigate the antiviral effect of galactose modified antisense RNA eukaryotic expression plasmid in Hepatitis B virus transgenic mice. Methods Gal-PL L was used as a liver-targeting vector and the eukaryotic expression recombinant plasmid (p CEP4 -a C) of antisense RNA of C region of hepatitis B virus was prepared as Gal-PL L - p CEP4 - a C. A total of 24 serum HBV DNA and HBsAg positive mice were randomly divided into Gal-PL L - p CEP4 - a C treatment group, Gal-PL L - p CEP4 control group and saline control group. The tail vein of the first day was injected with Gal-PL L - p CEP4 - a C, Gal - PL L - p CEP4 (100 μg / body) and an equal volume of normal saline to observe the changes of serum HBV DNA and HBs Ag before and after treatment. Results Serum HBV DNA negative rate was 6.5% (5/8) on day 2 of Gal-PL L - p CEP4 - a C treatment, and serum HBsAg was significantly decreased on day 7,14 and 21; - The serum HBVDNA of negative group (1/8) in CEP4 group was not changed to negative one in the normal saline group. There was no significant difference in serum HBsAg between the two groups before treatment (P> 0 .0 5). Conclusion Liver-targeted antisense RNA can inhibit HBV replication and antigen expression in HBV-infected mice