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目的研究特异性抑制呼吸道合胞病毒(respiratory syncytial virus,RSV)N基因的脱氧核酶DZ1133在小鼠体内对病毒复制和气道炎症的影响。方法RSV感染BALB/c小鼠滴鼻给予DZ1133及其变异体、反义寡核苷酸AS1133,空斑形成实验检测肺组织病毒滴度,RT-PCR检测病毒mRNA表达,支气管肺泡灌洗液白细胞计数,ELISA检测TNF-α、IL-12、IFN-γ和IL-10水平,肺组织病理学分析炎症情况。结果0.2、0.4mg和0.8mgDZ1133治疗组小鼠肺组织病毒滴度分别为(2.75±0.21)×105、(1.86±0.20)×105PFU/g和(1.02±0.22)×105PFU/g,与感染对照组小鼠(7.94±0.42)×105PFU/g比较明显下降(P<0.01),上述各剂量治疗组小鼠肺组织病毒mRNA表达与感染对照组比较分别下降30.51%、47.38%(P<0.05)和53.97%(P<0.01)。0.4mgDZ1133治疗降低RSV感染小鼠支气管肺泡灌洗液中白细胞总数,改善肺组织病理学损伤(P<0.05),对TNF-α、IL-12、IFN-γ和IL-10水平无显著性影响(P>0.05)。结论特异性脱氧核酶DZ1133在小鼠体内有效抑制RSV复制、减轻气道炎症,是有效的抗RSV途径。
Objective To investigate the effect of DZ1133, a specific inhibitor of respiratory syncytial virus (RSV) N gene, on virus replication and airway inflammation in mice. Methods DZ1133 and its variants were administered intranasally to BALB / c mice infected with RSV. AS1133 antisense oligonucleotide was used to detect the virus titer of lung tissue in plaque formation assay. The expression of viral mRNA was detected by RT-PCR. The bronchoalveolar lavage fluid leukocytes The levels of TNF-α, IL-12, IFN-γ and IL-10 were detected by ELISA. Inflammation was analyzed by histopathology. Results The titer of lung tissue in mice treated with 0.2, 0.4 and 0.8 mg DZ1133 were (2.75 ± 0.21) × 105, (1.86 ± 0.20) × 105 PFU / g and (1.02 ± 0.22) × 105 PFU / g, (7.94 ± 0.42) × 105 PFU / g decreased significantly (P <0.01). Compared with the control group, the expression of virus mRNA in lung tissue of mice in each dose group decreased by 30.51% and 47.38%, respectively (P <0.05) And 53.97% (P <0.01). 0.4mgDZ1133 treatment reduced the total number of leukocytes in bronchoalveolar lavage fluid of RSV-infected mice and ameliorated the pathological damage of lung tissue (P <0.05), but had no significant effect on the levels of TNF-α, IL-12, IFN-γ and IL-10 (P> 0.05). Conclusion The specific DNAzyme DZ1133 effectively inhibits RSV replication and ameliorates airway inflammation in mice and is an effective anti-RSV pathway.