干扰素α2经鼻给药预防小鼠感染甲型H1N1流感病毒的效果评价

Efficacy of intranasal administration of interferon α2 in preventing infection with influenza A (H1N1) virus

  • 摘要: 背景 频繁发生的呼吸道病毒疫情严重危害人类健康,干扰素等广谱抗病毒药物可能成为病毒流行初期的紧急预防措施,但现有研究缺乏系统性药效评估。目的 探究经鼻给予干扰素α2能否有效激活呼吸道免疫应答反应,并以甲型H1N1流感病毒构建感染模型,评估干扰素α2在预防呼吸道病毒感染中的潜在作用。方法 通过梯度设置干扰素α2的给药剂量和时间,采用经鼻途径对小鼠进行干预,监测肺部干扰素应答反应变化,确定最优给药条件。随后在该条件下对小鼠进行预防性给药,分析肺脏细胞因子表达变化,并进行甲型H1N1流感病毒攻毒实验,评价干扰素α2的保护效果。结果经鼻给予干扰素α2可诱导肺部干扰素应答反应,反应强度与给药剂量和时间显著相关,在给予2×105 U干扰素α2 2 h后达到峰值。采用该方案进行单次预防性给药,显著促进肺脏IL-28等抗病毒细胞因子的表达(P<0.05),并在小鼠接受致死剂量甲型H1N1流感病毒攻毒后显著降低上呼吸道病毒滴度(P<0.05),改善肺部水肿、出血等病理损伤(P<0.05),延长生存时间(P<0.01)。结论 经鼻给予干扰素α2能有效诱导肺部干扰素应答反应,为甲型H1N1流感病毒感染提供保护。本研究为干扰素在呼吸道病毒感染防治中的应用奠定基础。

     

    Abstract:
    Background The frequent outbreaks of respiratory viral infections pose a severe threat to human health. Broadspectrum antiviral agents such as interferons may serve as emergency prophylactic measures during the early stages of viral pandemics and epidemics, yet existing studies lack systematic efficacy evaluations.Objective To investigate whether intranasal administration of interferon α2 effectively activates respiratory immune responses, and evaluate the potential role of interferon α2 in preventing respiratory viral infections using influenza A (H1N1) virus infection model.Methods Mice were intranasally pre-treated with interferon α2 according to different administration schedules and dosage gradients. The changes in lung interferon responses were monitored to determine optimal administration conditions. Mice were subjected to preventive treatment under these conditions, followed by analyses of cytokine expression profiles in lungs, and infection with the influenza A (H1N1) virus to assess the protective efficacy of interferon α2.Results The results indicated that intranasal administration of interferon α2 induced dose- and time-dependent interferon responses in the lungs, and the peak was attained two hours after administering 2×105 U of interferon α2. Employing this administration regimen for a single-dose intranasal preventive treatment significantly upregulated antiviral cytokines including IL-28 in lungs (P < 0.05), and effectively reduced viral titers in upper respiratory tracts (P < 0.05), ameliorated pathological damage such as pulmonary edema and hemorrhage (P < 0.05) and extended survival in mice challenged with a lethal dose of influenza A (H1N1) virus (P < 0.01).Conclusion This study demonstrates that intranasal administration of interferon α2 induces an effective interferon response in the lungs, providing protection against influenza A (H1N1) virus infection, which lays a foundation for the application of interferons in the prevention and treatment of respiratory viral infections.

     

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