黄芩苷与利巴韦林联用体内外抗流感病毒作用

目的评价黄芩苷与利巴韦林联用体内外抗流感病毒作用,为其临床上联用提供实验依据。方法 CPE法和MTT法测定药物单用及联用对感染3种不同亚型流感病毒MD-CK细胞的保护效果,分别应用合并指数法(combination in-dex,CI)和MacSynergyⅡ分析法,分析黄芩苷与利巴韦林体外联用的相互作用。神经氨酸酶(NA)抑制试验测定黄芩苷对流感病毒NA活性的抑制作用。应用H1N1亚型流感病毒(FM1株)人工感染BALB/c小鼠模型,评价黄芩苷与利巴韦林联用对感染小鼠的保护作用。结果体外黄芩苷与利巴韦林联用对H1N1和H5N1病毒的抑制表现为相加作用,对H9N2病毒的抑制表现为协同作用。黄芩苷对3种亚型流感病毒NA的半数抑制浓度(IC50)在0.29～0.49 mmol.L-1范围。利巴韦林与黄芩苷联合给药与单独给药相比,提高感染小鼠的存活率,延长其存活时间。结论黄芩苷对流感病毒NA活性具有抑制作用。黄芩苷与利巴韦林在体外联用,对不同亚型流感病毒的抑制表现为相加或协同作用;二者联用对感染流感小鼠的保护效果明显优于单用。

Effects of the combination of baicalin and ribavirin on influenza A virus infection in vitro and in vivo

Aim To evaluate effects of the combination of baicalin and ribavirin on influenza A virus infection in cell culture and in mice,and provide experimental basis for their co-use clinically.Methods MTT and CPE assays were applied to test protective effects of baicalin and ribavirin against three different influenza virus subtypes in MDCK cells under the condition of used alone or in combination,respectively.CI analysis and MacSynergyⅡ analysis were applied to analyze interaction of baicalin and ribavirin in vitro,respectively.Neuraminidase inhibition assay was used to evaluate inhibitory effects of baicalin on the activity of influenza viral neuraminidases.The BALB/c mice infected with H1N1 virus were adopted to test protective effects of baicalin and ribavirin used alone or in combination.Results The combination of baicalin and ribavirin exhibited additive inhibitory activities against H5N1 and H1N1 viruses,and significant synergistic inhibitory activity against H9N2 virus in cell culture.The 50% effective inhibitory concentrations(IC50) of baicalin on the NAs from three different viruses ranged from 0.29 to 0.49 mmol·L-1.The treatment of ribavirin plus baicalin significantly improved survival rates and surviving times of mice infected with H1N1 virus,when compared with the treatment of either compound used alone.Conclusion Baicalin has some inhibitory effect on influenza viral neuraminidases.The combination of baicalin and ribavirin shows additive or synergistic inhibitory activity against different influenza viruses in vitro,depending on the tested virus subtypes.The treatment of ribavirin plus baicalin was more effective in influenza A infection in mice than either compound used alone.