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阿比朵尔对乳鼠致死性汉坦病毒感染及体外实验的疗效

Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro.

作者信息

Deng Hai-Ying, Luo Fan, Shi Li-Qiao, Zhong Qiong, Liu Ying-Juan, Yang Zhan-Qiu

机构信息

State Key Laboratory of Virology, Institute of Medical Virology, School of Medicine, Wuhan University, Wuhan 430071, China.

出版信息

Acta Pharmacol Sin. 2009 Jul;30(7):1015-24. doi: 10.1038/aps.2009.53. Epub 2009 Jun 8.

Abstract

AIM

Arbidol is an immunomodulator that was first developed in Russia. In this study, we report the antiviral activity of arbidol against Hantaan virus (HTNV) in vitro and in vivo.

METHODS

The antiviral activity of arbidol in vitro was determined by plaque-forming assay, ranging from 0.5 to 8 microg/mL. To investigate whether arbidol has an antiviral effect in vivo, suckling BALB/c mice infected with HTNV were treated with arbidol at 24 h before infection with a 5, 10 or 20 mg.kg(-1).d(-1), once per day, for 10 days. On day 12 and 28 post infection (pi), histopathological changes and viral antigen were detected. On days 4, 8, 12, and 16 pi, the viral load of target organs and serum TNF-alpha levels of arbidol-treated animals were determined.

RESULTS

Arbidol was found to have potent inhibitory activity against HTNV when added in vitro before or after viral infection, with a 50% inhibitory concentration (IC(50)) of 0.9 and 1.2 microg/mL, respectively. The 50% lethal dose (LD(50)) of arbidol for suckling mice was 78.42 mg.kg(-1).d(-1). Oral administration of arbidol increased both survival rate and mean time to death (MTD). Treatment with arbidol reduced histopathological changes, decreased viral load and viral antigen levels, and modulated the level of serum TNF-alpha.

CONCLUSION

Arbidol has the ability to elicit protective antiviral activity against HTNV in vivo and in vitro.Acta Pharmacologica Sinica (2009) 30: 1015-1024; doi: 10.1038/aps.2009.53; published online 8 June 2009.

摘要

目的

阿比朵尔是一种最初在俄罗斯研发的免疫调节剂。在本研究中,我们报告了阿比朵尔在体外和体内对汉坦病毒(HTNV)的抗病毒活性。

方法

通过空斑形成试验测定阿比朵尔在体外的抗病毒活性,浓度范围为0.5至8微克/毫升。为研究阿比朵尔在体内是否具有抗病毒作用,对感染HTNV的乳鼠在感染前24小时用阿比朵尔以5、10或20毫克·千克-1·天-1进行治疗,每天一次,共10天。在感染后第12天和28天,检测组织病理学变化和病毒抗原。在感染后第4、8、12和16天,测定阿比朵尔治疗动物的靶器官病毒载量和血清肿瘤坏死因子-α水平。

结果

发现阿比朵尔在病毒感染前或感染后体外添加时对HTNV具有强大的抑制活性,50%抑制浓度(IC50)分别为0.9和1.2微克/毫升。阿比朵尔对乳鼠的50%致死剂量(LD50)为78.42毫克·千克-1·天-1。口服阿比朵尔可提高生存率和平均死亡时间(MTD)。阿比朵尔治疗可减轻组织病理学变化,降低病毒载量和病毒抗原水平,并调节血清肿瘤坏死因子-α水平。

结论

阿比朵尔在体内和体外均具有对HTNV引发保护性抗病毒活性的能力。《中国药理学报》(2009年)30卷:1015 - 1024页;doi: 10.1038/aps.2009.53;2009年6月8日在线发表。

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