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栀子苷对甲型H1N1流感病毒的抑制作用

张耘实, 祁贤, 卢协勤, 刘星, 冯旰珠

张耘实, 祁贤, 卢协勤, 刘星, 冯旰珠. 栀子苷对甲型H1N1流感病毒的抑制作用[J]. 中国药科大学学报, 2016, 47(2): 204-209. DOI: 10.11665/j.issn.1000-5048.20160213
引用本文: 张耘实, 祁贤, 卢协勤, 刘星, 冯旰珠. 栀子苷对甲型H1N1流感病毒的抑制作用[J]. 中国药科大学学报, 2016, 47(2): 204-209. DOI: 10.11665/j.issn.1000-5048.20160213
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ZHANG Yunshi, QI Xian, LU Xieqin, LIU Xing, FENG Ganzhu. Inhibitory effect of geniposide against influenza A/H1N1 virus[J]. Journal of China Pharmaceutical University, 2016, 47(2): 204-209. DOI: 10.11665/j.issn.1000-5048.20160213
Citation: ZHANG Yunshi, QI Xian, LU Xieqin, LIU Xing, FENG Ganzhu. Inhibitory effect of geniposide against influenza A/H1N1 virus[J]. Journal of China Pharmaceutical University, 2016, 47(2): 204-209. DOI: 10.11665/j.issn.1000-5048.20160213
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栀子苷对甲型H1N1流感病毒的抑制作用

  • 1.

    南京医科大学第二临床医学院

  • 2.

    江苏省疾病预防控制中心

  • 3.

    南京医科大学第二附属医院药剂科

  • 4.

    南京医科大学第二附属医院呼吸科

基金项目: 国家自然科学基金资助项目(No.81470209)；江苏省中医药管理局项目(No.LZ13228)；南京市卫生局医药科技发展资助项目(No.YKK13176)

Inhibitory effect of geniposide against influenza A/H1N1 virus

摘要

    摘要
  • 摘要: 为探讨栀子苷对甲型H1N1病毒的抑制效应，进行了相关体内外实验研究。体外实验中采用MTT法判定栀子苷对MDCK细胞的毒性作用。以帕拉米韦为阳性对照药，根据MTT比色值，观察栀子苷对甲型H1N1流感病毒感染的MDCK细胞的细胞病变效应(cytopathic effects，CPE)，计算不同给药方式(预防给药、直接灭活及治疗给药)及不同药物剂量干预下，栀子苷对甲型H1N1流感病毒的抑制效率；体内实验以甲型H1N1流感病毒感染ICR小鼠，建立甲型H1N1流感病毒小鼠肺炎模型，比较栀子苷不同剂量干预下，小鼠肺指数、肺组织病理学检查及小鼠存活率。实验结果显示，栀子苷的细胞毒性小，其TD50大于1 040 μmol/L；栀子苷在预防、直接灭活及治疗给药方式下，对甲型H1N1流感病毒感染的MDCK细胞抗病毒EC50分别为91.90、96.25和87.68 μmol/L，对CPE有明显抑制作用；栀子苷可显著降低甲型H1N1流感病毒感染小鼠的肺指数、减轻肺组织炎症损伤、降低小鼠死亡率、延长生存时间。实验结果表明，栀子苷在体外能有效抑制甲型H1N1流感病毒对MDCK细胞的CPE，在体内能有效保护甲型H1N1流感病毒对小鼠肺部的攻击作用，可能为流感病毒的防治提供一个新的选择。
    Abstract: The aim of this study was to explore the protective effects of geniposide against Influenza A(H1N1)pdm09 virus in vitro and in vivo. In vitro, geniposide was administered as a precaution drug, a direct deactivation drug or a treatment drug at different doses. Peramivir was applied as a positive control. The quantitative colorimetric MTT assay was applied to test both the cytotoxicity of geniposide on Madin-Darby Canine Kidney(MDCK)cells and the cytopathogenic effect(CPE)of geniposide on MDCK cells infected by influenza A(H1N1)virus. The viral inhibitory rate of geniposide on NT0901 was also calculated. In vivo, we presented a mouse model of influenza A(H1N1)pdm09 virus infection. Geniposide(5, 10, or 20 mg/kg)or peramivir(30mg/kg)were used as treatment procedures. Lung index and the survival rate were calculated to evaluate the therapeutic effects of geniposide or peramivir on NT0901-infected mice. Haematoxylin and eosin(H&E)stain was used to access the pathological alterations of lung tissues. The study in vitro demonstrated that the TD50(median toxic dose)of geniposide was higher than 1 040 μmol/L. Besides, the EC50(concentration for 50% of maximal effect)of geniposide administered for precaution, direct deactivation and therapy were 91. 90, 96. 25, 87. 68 μmol/L, respectively. These results suggested that geniposide could block the damage of NT0901 on MDCK cells in a dose-dependent manner. The results in vivo showed that geniposide could significantly alleviate the lung index elevation and inflammatory responses in lung tissues induced by NT0901, reduce the mortality of infected mice and extend their survival time. In conclusion, our investigation indicates that geniposide is highly effective in inhibiting cytopathogenic effect and acute lung injury caused by influenza A(H1N1)pdm09 virus. Geniposide may be a potential therapeutic agent for the suppression of influenza virus.
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  • 刊出日期:  2016-04-24

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