短发卡RNA对细胞及小鼠体内甲型流感病毒抑制作用研究  

Inhibitory effect of hairpin RNA on influenza A virus in cells and mice

作　　者：史亮 尹沈慧 任浩 高荣 赵俭 马壮 孙文武 曹建平 SHI Liang;YIN Shen-hui;REN Hao;GAO Rong;ZHAO Jian;MA Zhuang;SUN Wen-wu;CAO Jian-ping(Department of Respiratory and Critical Care Medicine,General Hospital of Northern Theater Command,Shenyang 110016,China;Department of Naval Medicine,Naval Medical University,Shanghai 200433,China;Department of Respiratory,Joint Logistic Support Unit 968 Hospital,Jinzhou 121001,China)

机构地区：[1]北部战区总医院呼吸与危重症医学科,辽宁沈阳110016 [2]海军军医大学海军医学系,上海200433 [3]解放军联勤保障部队第九六八医院呼吸科,辽宁锦州121001

出　　处：《临床军医杂志》2020年第1期1-4,共4页Clinical Journal of Medical Officers

基　　金：中国人民解放军“十二五”科研基金(CSY14C005)。

摘　　要：目的探讨短发卡RNA(shRNA)对细胞及小鼠体内甲型流感病毒(IVA)抑制作用。方法合成12种针对IVA保守区域的shRNA,观察这些shRNA对IVA在细胞中复制的影响。将转染了shRNA的质粒以气溶胶形式雾化吸入小鼠,然后以流感病毒感染小鼠并检测小鼠肺组织流感病毒载量。结果转染了质粒PLKD-M-121、PLKD-M-935、PLKD-NP-391、PLKDNP-1291、PLKD-PA-1365、PLKD-PA-1645的犬肾细胞中IVA载量均显著低于对照组及空质粒组(P <0. 05)。染PLKD-NP-391小鼠肺部IAV载量明显低于对照组和空质粒组(P <0. 05)。结论针对流感病毒基质蛋白(M2)、核壳体蛋白(NP)和聚合酶A(PA)片段的shRNA可以抑制流感病毒的产生,以气溶胶形式吸入聚乙烯亚胺/PLKD-NP-391复合物可以抑制小鼠肺部流感病毒的产生。Objective To investigate the inhibitory effect of short hairpin RNA( shRNA) on influenza A virus( IVA) in cells and mice.Methods To synthesize 12 shRNA specific to IVA conserved regions and observe the effect of these shRNA on IVA replication in cells. The shRNA-transfected plasmids were aerosolized into mice,then infected with influenza virus and tested for influenza viral load in lung tissues. Results The IVA load in MDCK cells transfected with plasmids PLKD-M-121,PLKD-M-935,PLKD-NP-391,PLKDNP-1291,PLKD-PA-1365 and PLKD-PA-1645 was significantly lower than that in the control group and the empty plasmid group( P <0. 05). The pulmonary IAV load of PLKD-NP-391 mice was significantly lower than that of the control group and the empty plasmid group( P < 0. 05). Conclusion ShRNA targeting influenza virus matrix protein( M2),nucleocapsid protein( NP) and polymerase A( PA) fragments inhibited influenza virus production,and inhalation of the polythelenimine/PLKD-NP-391 complex in aerosol form inhibited influenza virus production in mice lungs.

关 键 词：甲型流感病毒 RNA干扰 基质蛋白2 核壳体蛋白 聚合酶A 短发卡RNA 

分 类 号：R346[医药卫生—基础医学]