金贝口服液抗小鼠甲型H1N1流感病毒及继发性肺炎链球菌感染作用研究

Study on the effects of Jinbei oral liquid against influenza A H1N1 virus and secondary Streptococcus pneumoniae infection of mice

目的研究金贝口服液体内抗小鼠甲型H1N1流感病毒及继发性肺炎链球菌感染的作用,为其临床应用提供参考。方法以磷酸奥司他韦胶囊(25.6 mg/kg)为阳性对照进行实验。通过滴鼻含0.8个半数致死量(LD_(50))的H1N1病毒液复制小鼠甲型H1N1流感病毒感染模型,以体质量、肺指数、肺病毒载量、肺组织病理形态变化以及血清中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-6水平为指标,考察15.6、7.8、3.9 mL/kg金贝口服液体内抗甲型H1N1流感病毒的作用。通过滴鼻含0.5个LD_(50)的H1N1病毒液和含1×10^(9)个菌落形成单位的肺炎链球菌液复制继发性肺炎链球菌感染模型,以小鼠死亡情况、肺指数、鼻腔和肺部细菌载量以及血清中干扰素β(IFN-β)、IL-17、IL-23水平为指标,考察15.6 mL/kg金贝口服液体内抗继发性肺炎链球菌感染的作用。结果15.6、7.8 mL/kg金贝口服液给药6 d后,均可显著升高甲型H1N1流感病毒感染小鼠异常降低的体质量,显著降低其异常升高的肺指数及血清中TNF-α、IL-1β、IL-6水平(P<0.05),显著降低其肺部病毒载量(P<0.05),减轻其肺组织病变程度。15.6 mL/kg金贝口服液还可显著延长病毒-细菌共感染小鼠的存活时间(P<0.05),降低其死亡率;显著升高其异常降低的体质量和血清中IL-17、IL-23水平(P<0.05),显著降低其鼻腔和肺部细菌载量以及血清中异常升高的IFN-β水平(P<0.05)。结论金贝口服液具有一定的抗小鼠甲型H1N1流感病毒感染作用,且能通过恢复17型免疫功能帮助机体抵抗继发性肺炎链球菌感染。

OBJECTIVE To study the effects of Jinbei oral liquid against influenza A H1N1 virus and secondary Streptococcus pneumoniae infection of rats,and to provide reference for its clinical application.METHODS Oseltamivir phosphate capsule(25.6 mg/kg)was used as a positive control.Influenza A H1N1 virus infection model of mice was established by nasal drops of H1N1 virus containing 0.8 median lethal dose(LD_(50)).The body mass,lung index,lung viral load,pathological changes of lung tissue,and serum levels of tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β)and IL-6 were used as indexes to investigate the anti-H1N1 virus effect of 15.6,7.8 and 3.9 mL/kg Jinbei oral liquid in vivo.The model of secondary S.pneumoniae infection was established by nasal drops of H1N1 virus solution containing 0.5 LD_(50) and S.pneumoniae solution containing 1×10^(9) colony forming units.The death,lung index,nasal and lung bacterial load,serum levels of interferon-β(IFN-β),IL-17 and IL-23 were used as indexes to investigate the effects of 15.6 mL/kg Jinbei oral liquid against secondary S.pneumoniae infection.RESULTS After 6 days of administration,both 15.6 and 7.8 mL/kg Jinbei oral liquid significantly increased the abnormally reduced body weight of influenza A H1N1 virus infected mice,significantly reduced the abnormally increased lung index and serum levels of TNF-α,IL-1β,IL-6(P<0.05);it also significantly reduced the viral load in the lung(P<0.05)and alleviated the degree of lung tissue lesions.At the same time,15.6 mL/kg Jinbei oral liquid significantly prolonged the survival time of mice co-infected with virus and bacteria(P<0.05)and reduced the mortality rate;it also significantly increased the abnormally reduced body weight and serum levels of IL-17 and IL-23(P<0.05),while reduced the nasal and lung bacterial loads and the abnormally increased serum level of IFN-β(P<0.05)CONCLUSIONS Jinbei oral liquid has a certain anti-influenza A H1N1 virus infection effect of rats and can help the body resist secondary S.pneumoniae infection by restoring the type 17 antibacterial immune function.