RNA干扰体内抑制HBeAg表达

RNAi inhibition of HBeAg expression in vivo

目的在机体水平观察小干扰RNA(siRNA)对HBeAg表达的影响。方法通过尾静脉注射1.5倍的HBV真核表达质粒pHBV1.5建立小鼠急性乙型肝炎病毒感染模型,再将其与针对乙型肝炎病毒核心区的siRNA表达载体(psiHBV4)共注射,于注射后第6天取血测HBeAg的表达,并用RT-PCR检测肝组织HBV prec/c mRNA转录子的水平。结果注射后第6天血清中,HBsAg、HBeAg在造模组中高表达。psiHBV4干扰组中HBeAg的表达受到了明显的抑制,与对照组相比有显著差异(P<0.05),RT-PCR显示肝内HBV prec/c mRNA水平亦明显降低,而无关干扰对照组则无相应的干扰作用。结论RNAi能特异,高效的抑制小鼠体内HBeAg的表达,为乙型肝炎的治疗带来了新的希望。

Objective To observe the effects of the RNA interference-mediated inhibition on HBeAg expression in the animal model. Methods Hydrodynamic injection of naked plasmid was used to construct a mouse model of acute hepatitis B vires infection. Then, interference group was injected with pHBV1.5 and psiHBVd plasmid that expressing HBV-C specific short hairpin RNA. After six days, the mice were sacrificed to collect the blood and livers. MEIA was used to measure the concentration of HBsAg and HBeAg in the serum; RT-PCR was used to detect the expression of HBV prec/c mRNA in the liver. Results Six days after injection, the HBeAg expression in the serum of the interference group was suppressed effectively compared with the control group （ P 〈 0.05）. RT-PCR showed that the expression of HBV prec/c mR- NA in the liver of the interference group was inhibited. While the HBeAg expression in the sera and the HBV prec/c mRNA in the liver of irrelevant interference group were not inhibited. Conclusion RNAi specifically and effectively inhibits the expression of HBeAg, which brings a new hope for therapy of HBV.