重组人干扰素α1b体外抗3型腺病毒的药效学及作用机制初步研究  

In Vitro Efficacy and Preliminary Mechanism of Recombinant Human Interferon α1b Against Adenovirus Type 3

作　　者：聂思怡 王召静 李欢欢 徐晨 姚文兵[1] NIE Si-Yi;WANG Zhao-Jing;LI Huan-Huan;XU Chen;YAO Wen-Bing(College of Life Science and Technology,China Pharmaceutical University,Nanjing 210009;Beijing Tri-Prime Gene Pharmaceutical Co.,Ltd,Beijing 102600,China)

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京210009 [2]北京三元基因药业股份有限公司,北京102600

出　　处：《生物技术通讯》2020年第3期285-291,共7页Letters in Biotechnology

摘　　要：目的:研究重组人干扰素α1b(IFNα1b)体外抗3型腺病毒(HAdV3)的药效,并探讨IFNα1b与利巴韦林的联合效应。方法:噻唑蓝(MTT)法测定IFNα1b、利巴韦林对A549细胞的毒性,乳酸脱氢酶(LDH)法和AnnexinV/PI双染法检测IFNα1b抗HAdV3感染的作用效果;采用MTT法与利巴韦林进行比较,同时检测IFNα1b和利巴韦林联用时的体外药效和联合效应。结果:LDH法测得IFNα1b抗HAdV3的半数有效浓度(EC50)为2.6±0.8 ng/mL,可显著降低感染细胞凋亡率(P<0.001)。MTT法测得IFNα1b和利巴韦林的治疗指数(TI)分别为>100 000和28.3。IFNα1b与利巴韦林小剂量联用时具有协同作用,可提高细胞存活率,降低单药用量。结论:IFNα1b体外对HAdV3有较强的抑制作用,且与利巴韦林在一定浓度范围内呈协同作用。Objective:To study the efficacy of recombinant human interferon α1 b(IFNα1 b) against adenovirus type 3(HAdV3) in vitro and to investigate the combination effects of IFNα1 b combined with ribavirin.Methods:The cytotoxicity of IFNα1 b and ribavirin on A549 cells were determined by MTT colorimetric method, antiviral effect of IFNα1 b was measured by LDH method and double-labeling with AnnexinV and PI, ribavirin was used for comparison by MTT method. IFNα1 b and ribavirin were combined in order to determine the inhibitory activity and combination effects.Results:The EC50 of IFNα1 b measured by LDH method was 2.6± 0.8 ng/mL, and the late apoptosis rate of IFNα1 b-treated groups were significantly reduced(P<0.001). The therapeutic index(TI) of IFNα1 b and ribavirin measured by MTT method were >100 000 and 28.3 respectively. IFNα1 b worked synergistically with ribavirin in small doses and the combination showed an enhanced inhibitory effect and could reduce the dose of individual drugs.Conclusion:IFNα1 b has a significant anti-HAdV3 activity in vitro, and showed a synergistic effect when combined with ribavirin in a certain concentration range.

关 键 词：重组人干扰素Α1B 3型腺病毒 利巴韦林 协同作用 体外药效学 

分 类 号：R978.7[医药卫生—药品]