利巴韦林具有广谱抗病毒作用,甘草酸具有抗炎、免疫调节和抗病毒活性。为了增强抗病毒药效、减少利巴韦林的不良反应,本文对二者联合应用的抗流感病毒效果进行了研究。以H1N1亚型流感病毒人工感染BALB/c小鼠,建立小鼠病毒性肺炎模型。以小鼠存活率、肺指数抑制率和肺病毒滴度等为评价指标,考察甘草酸和利巴韦林联用对感染H1N1亚型流感病毒小鼠的保护作用。结果表明,甘草酸和利巴韦林联用能显著抑制H1N1亚型流感病毒引起的小鼠肺炎实变,对攻毒后第5天小鼠肺指数抑制率为36%;两药联用对感染小鼠有协同保护作用,甘草酸(50 mg·kg^-1·d^-1)与利巴韦林(40 mg·kg^-1·d^-1)联用对感染小鼠的保护率达到100%,显著高于病毒对照组和单一药物组(P〈0.01),协同值为36。两药联用显著降低感染小鼠肺组织的病毒滴度(P〈0.01),同时对病毒感染诱导的小鼠血浆炎症因子IL-6(P〈0.01)、TNF-α(P〈0.01)和IL-1β(P〈0.05)的升高具有显著抑制作用。结果提示,甘草酸和利巴韦林联用对感染H1N1亚型流感病毒小鼠具有协同保护作用,在临床上具有重要的应用价值。
Ribavirin is a broad-spectrum antiviral agent and glycyrrhizin has activities of anti-inflammation, immunoregulation and anti-viral infections. To enhance antiviral efficacy and weaken side-effects of ribavirin, antiviral effects of the combination of glycyrrhizin and ribavirin were studied in the present study. Firstly, a mouse model of viral pneumonia was established by inoculation of influenza H1N1 virus. Protective effects of glycyrrhizin and ribavirin used alone or in combination against H1N1 virus infection in mice were evaluated based on the survival rate, lung index and virus titer in lungs of mice. Results showed that the combination of glycyrrhizin and ribavirin significantly inhibited the lung consolidation with a 36% inhibition ratio on the lung swell of infected mice. The combination of the two drugs exhibited synergetic effects on survival of infected mice. The combination of 50 mg·kg^-1·d^-1 glycyrrhizin and 40 mg·kg^-1·d^-1 ribavirin resulted a 100% protection for infected mice with a synergetic value of 36, which was significantly higher than the control group and each drug alone. This combination also resulted a significant drop of lung virus titer (P〈0.01), as well as inhibition on the production of proinflammatory cytokines IL-6 (P〈0.02), TNF-α (P〈0.01) and 1L-1β (P〈0.05) induced by virus infection compared to the control. The treatment of ribavirin plus glycyrrhizin was more effective in influenza A infection in mice than either compound used alone, which suggested a potential clinical value of the combination of the two agents.