siRNA的组合介导乙肝病毒复制的小鼠更大的抑制。

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Cell Biochem Biophys. 2014 Jul;69(3):641-7. doi: 10.1007/s12013-014-9846-2.
siRNA combinations mediate greater suppression of hepatitis B virus replication in mice.Li G1, Fu L, Jiang J, Ping Y, Huang Y, Wang Y.
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• 1Department of Clinical Laboratory, the Affiliated First Hospital of Harbin Medical University, Harbin, 150001, China.
  

AbstractHepatitis B virus (HBV) infection is a major world-wide health problem. The major obstacles for current anti-HBV therapy are the low efficacy and the occurrence of drug resistant HBV mutations. Recent studies have demonstrated that combination therapy can enhance antiviral efficacy and overcome shortcomings of established drugs. In this study, the inhibitory effect mediated by combination of siRNAs targeting different sites of HBV in transgenic mice was analyzed. HBsAg and HBeAg in the sera of the mice were analyzed by enzyme-linked immunoadsorbent assay, HBV DNA by real-time PCR and HBV mRNA by RT-PCR. Our data demonstrated that all the three siRNAs employed showed marked anti-HBV effects. The expression of HBsAg and the replication of HBV DNA could be specifically inhibited in a dose-dependent manner by siRNAs. Furthermore, combination of siRNAs compared with individual use of each siRNA, exerted a stronger inhibition on antigen expression and viral replication, even though the final concentration of siRNA used for therapy was the same. Secreted HBsAg and HBeAg in the serum of mice treated with siRNA combination were reduced by 96.7 and 96.6 %, respectively. Immunohistochemical detection of liver tissue revealed 91 % reduction of HBsAg-positive cells in the combination therapy group. The combination of siRNAs caused a greater inhibition in the levels of viral mRNA and DNA (90 and 87.7 %) relative to the control group. It was noted that the siRNA3 showed stronger inhibition of cccDNA (78.6 %). Our results revealed that combination of siRNAs mediated a stronger inhibition of viral replication and antigen expression in transgenic mice than single siRNAs.


PMID:24549857 [PubMed - in process] 细胞生物化学和生物物理学。2014年七月，69（3）：641-7。 DOI：10.1007/ s12013-014-9846-2。
siRNA的组合介导乙肝病毒复制的小鼠更大的抑制。
李G1，富升，江Ĵ，平Y，黄Y，王华
作者信息

    临床教研室实验室，哈尔滨医科大学，哈尔滨，150001，中国附属第一医院。

摘要

乙型肝炎病毒（HBV）感染是一个主要的全球性健康问题。对于目前的抗乙肝病毒治疗的主要障碍是低的疗效和耐药的HBV基因突变的发生。最近的研究表明，联合治疗可提高抗病毒疗效和克服的确立药物的缺点。在这项研究中，通过靶向的转基因小鼠的不同位点的HBV的siRNA的组合介导的抑制效果进行了分析。 HBsAg和HBeAg的小鼠的血清，用酶联免疫吸附法，HBV DNA通过实时PCR和HBV的mRNA，通过RT-PCR进行分析。我们的数据表明，使用所有三个siRNA的表现显着的抗HBV作用。乙肝表面抗原的表达和HBV-DNA的复制可以以剂量依赖的方式通过的siRNA可以特异性抑制。此外，siRNA的组合与单独使用各自的siRNA相比，施加在抗原表达和病毒复制的强抑制作用，即使siRNA的最终浓度用于治疗是一样的。 ，分泌的HBsAg和HBeAg的siRNA组合治疗的小鼠的血清中分别降低96.7和96.6％，分别。免疫组化检测肝组织发现91％以上的还原HBsAg阳性细胞的联合治疗组中。 siRNA的结合在病毒mRNA和DNA（90和87.7％）相对于对照组的水平造成了更大的抑制。据指出，该siRNA3具有更强的抑制cccDNA的（78.6％）的。我们的研究结果显示，siRNA的该组合在转基因小鼠比单一的siRNA介导的较强的抑制病毒复制和抗原表达。

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