金刚烷胺修饰物对禽流感（H5N1）病毒的抑制作用

doi:吉林省科技厅农业重大科技专项基金资助课题

金刚烷胺修饰物对禽流感（H₅N₁）病毒的抑制作用

徐坤¹，侯雷¹，杨松涛²，王宏芳¹，吴新宇¹ ,张秀芝¹，李娟¹，李静¹，夏咸柱²

1.吉林大学公共卫生学院卫生毒理学教研室，吉林长春 130021；2.解放军军事医学科学院军事兽医研究所,吉林长春 130062

收稿日期:2006-11-06 修回日期:1900-01-01 出版日期:2007-09-28 发布日期:2007-09-28
通讯作者: 李娟；李静

Inhibitory effect of modified amantadine on avian influenza(H₅N₁) virus

XU Kun¹,HOU Lei¹,YANG Song-tao²,WANG Hong-fang¹,WU Xin-yu¹,ZHANG Xiu-zhi¹,LI Juan¹,LI Jing¹,XIA Xian-zhu²

1.Department of Toxicology, School of Public Health,Jilin University,Changchun 130021,China;2.Institute of Military Veterinary,Academy of Military Medical Sciences,Changchun 130062,China

Received:2006-11-06 Revised:1900-01-01 Online:2007-09-28 Published:2007-09-28
Contact: LI Juan；LI Jing

摘要/Abstract

摘要： 目的：寻找高效低毒的抗禽流感病毒药物。方法：体外实验选用狗肾细胞（MDCK），实验分为正常对照组、病毒对照组和受试化合物组，采用细胞病变法结合MTT法检测金刚烷胺修饰物（NAM）对MDCK细胞的半数中毒浓度、对禽流感病毒的半数抑制浓度和治疗指数；体内实验采用NAM对禽流感病毒H₅N₁亚型小鼠感染模型的治疗实验，检测小鼠的死亡率、存活率、死亡保护率和延长生命率。结果：体外实验，NAM对MDCK细胞的最大无毒浓度为235.09 mg•L^-1，半数致死浓度为1582.78 mg•L^-1，NAM对禽流感病毒半数抑制浓度（IC₅₀）为15.32 mg•L^-1，治疗指数（TI,103.31)高于金刚烷胺对照组(TI,48.48)；体内实验，NAM 100 mg•kg^-1剂量组对H₅N₁感染小鼠的死亡率（12.5%）明显低于病毒对照组小鼠死亡率(87.5%)（P<0.05），平均生存日数（13.38 d）明显高于病毒对照组平均生存日数（9.63 d）（P<0.05），肺炎抑制率（99.15%）和生命延长率（26.79%）均高于金刚烷胺对照组肺炎抑制率（69.18%）和生命延长率（13.39%）(P<0.05)。结论：NAM体外毒性和抗病毒活性均优于阳性对照金刚烷胺；体内抗病毒活性较好，可显著降低禽流感病毒感染小鼠的死亡率、提高平均生存日数和延长生命率。

关键词: 金刚烷胺, 抗病毒活性

Abstract: Objective To screen efficient anti-influenza A (H₅N₁) medicine with low toxicity.Methods Normal control group,virus control group and test group were included in this study .The inhibitory effect and cytotoxicity of modified amantadine (NAM) on H₅N₁ virus and MDCK cells were detected by MTT and cytopatric effect (CPE) assay,respectively.The therapy index (TI) and 50% cell-inhibitory concentration (IC₅₀) were calculated.The mice infected with H₅N₁ virus were administered with NAM.The death rate,survival rate,death protection rate and prolong survival rate were calculated.Results The maximal no cytoxicity concentration and 50% cytoxicity concentration of NAM on MDCK cells were 235.09 mg•L^-1 and 1582.78 mg•L^-1,respectively.The IC₅₀ and TI of NAM on H₅N₁ virus were 15.32 mg•L^-1 and 103.31,respectively.The death rate (12.5%) in NAM 100 mg•kg^-1 group was significantly lower than that in virus control group (87.5%)(P<0.05),the mean survival days (13.38 d) was significantly higher than that in virus control group (9.63 d)(P<0.05),both inhibitory rate of pneumonia (99.15%) and prolongation survival rate (26.79%) were higher than those in amantadine group(69.18% and 13.39%)(P<0.05).Conclusion NAM has better antivirus activity and lower toxicity,compared with amantadine in vitro.NAM can significantly decrease mortality,increase average survival days and prolongation survival rate in vivo.

Key words: amantadine, anti-virus activity

中图分类号:

R978.7

徐坤，侯雷，杨松涛，王宏芳，吴新宇 ,张秀芝，李娟，李静，夏咸柱. 金刚烷胺修饰物对禽流感（H₅N₁）病毒的抑制作用[J]. J4, 2007, 33(5): 863-866.

XU Kun,HOU Lei,YANG Song-tao,WANG Hong-fang,WU Xin-yu,ZHANG Xiu-zhi,LI Juan,LI Jing,XIA Xian-zhu. Inhibitory effect of modified amantadine on avian influenza(H₅N₁) virus[J]. J4, 2007, 33(5): 863-866.

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金刚烷胺修饰物对禽流感（H₅N₁）病毒的抑制作用

Inhibitory effect of modified amantadine on avian influenza(H₅N₁) virus

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