蜜炼川贝枇杷膏对甲型H1N1流感病毒性肺炎小鼠的影响及相关机制研究

Effects and Mechanisms of Milian Chuanbei Pipa Gao on Viral Pneumonia Mice Induced by Influenza A Virus

目的研究蜜炼川贝枇杷膏对甲型H1N1流感病毒性肺炎小鼠的影响及其机制。方法将BABL/c小鼠随机分为正常对照组、病毒对照组、利巴韦林组(0.10 g·kg^(-1))和蜜炼川贝枇杷膏高、中、低剂量组(6.60、3.30、1.65 g·kg^(-1)),灌胃7 d后经滴鼻感染复制甲型H1N1流感病毒性肺炎小鼠模型。继续给药5 d,感染后第5天测定肺指数和肺病毒载量,计算小鼠死亡保护率、平均生存时间和延长生命率,观察肺组织病理并评分,酶联免疫吸附试验测定呼吸道和肠道黏膜中分泌性免疫球蛋白A(Secretory immunoglobulin A,sIgA)和血清中免疫球蛋白G(Immunoglobulin G,IgG)的含量。结果蜜炼川贝枇杷膏预防给药能明显降低肺炎小鼠的肺指数和肺病毒载量(P<0.05,P<0.01);高、中剂量组能明显减轻肺部炎症程度(P<0.01);一定程度上改善肺炎小鼠的死亡保护率和延长生命率(P>0.05);高、低剂量组能提高肺泡灌洗液、鼻咽冲洗液、肠道冲洗液中sIgA和血清中IgG的含量(P<0.01)。结论蜜炼川贝枇杷膏对甲型H1N1流感病毒性肺炎小鼠有预防保护作用,其机制可能与抑制病毒复制和激发黏膜免疫有关。

Objective To observe the effects and mechanisms of Milian Chuanbei Pipa Gao(PPG) on viral pneumonia mice induced by influenza A virus(IAV mice).MethodsBABL/c mice were randomly divided into a normal control group(NC),a IAV control group(IAV-C),a ribavirin group(0.10 mg·kg^(-1))and 3 PPG groups(6.60,3.30,1.65 g·kg^(-1)). Mice were anesthetized and intranasally challenged with A/FM/1/47(FM1,H1 N1)after7 days of intragastric administration. On the 5 th day post-infection,10 mice per group were killed to collect related sample,the lung index,and viral load were measured,and death prevention rate,mean survival time and life prolongation rate were observed. The pathological changes of lung tissue were examined by HE. The levels of secretory immunoglobulin A(sIgA) and immunoglobulin G(IgG) were detected by enzyme linked immunosorbent assay(ELISA).ResultsCompared with IAV-C,PPG can significantly reduce the lung index and virus load(P<0.05,P<0.01). The high-dose and medium-dose PPG groups could significantly alleviate the pathological changes of lung(P<0.01),and partly prolong the average survival time and cut down the mortality rate of mice(P>0.05).The high-dose and low-dose PPG groups could increase the level of sIgA and IgG in bronchoalveolar lavage fluid,nasopharynx lavage fluid and intestinal lavage fluid(P<0.01).ConclusionPPG may be able to provide protection against IVA infection in mice and the mechanism is related to the inhibition of virus replication and activation of mucosal immunity.