【目的】观察黄芪甲苷脂质体对甲型流感病毒感染小鼠的治疗作用及机制。 【方法】将50只BALB/c小鼠随机分为正常组（10只） 和造模组 （40只） 。造模组小鼠经鼻滴注A/PR/8/34 （H1N1） 流感病毒液。将造模小鼠随机分为模型组，奥司他韦组，黄芪甲苷脂质体高、低剂量组，每组10只。感染2 h后灌胃给药，连续5 d。观察小鼠外观，评估小鼠体质量、存活情况、肺指数、肺组织病毒载量，苏木素-伊红 （HE） 染色法观察肺组织病理，定量聚合酶链反应 （qPCR） 法检测肺组织中单核细胞趋化因子1 （MCP-1） 、巨噬细胞炎性蛋白1β （MIP-1β） 、干扰素γ （IFN-γ） 、CXC族趋化因子配基1 （CXCL-1） 、白细胞介素（IL） -6、IL-1β mRNA表达水平，酶联免疫吸附分析 （ELISA） 检测小鼠肺组织中粒细胞-巨噬细胞集落刺激因子 （GM-CSF） 、分泌调节活化因子 （RANTES） 含量。 【结果】与正常组比较，模型组小鼠体质量下降、存活时间缩短一半 （P＜0.001） 、肺指数显著上升 （P＜0.001） 、肺组织病毒载量显著升高 （P＜0.001） ，肺组织MIP-1β、IFN-γ、CXCL-1、IL-6、IL-1β、MCP-1 mRNA 表达水平显著升高 （P＜0.05或P＜0.001） ，病理可见肺组织结构破坏；与模型组比较，黄芪甲苷脂质体高剂量组小鼠体质量下降减缓，存活时间和存活率升高 （P＜0.05） ，肺指数显著下降 （P＜0.05） ，肺组织病毒载量下降 （P＜0.001） ，肺组织MIP-1β、IFN-γ、CXCL-1、IL-6、IL-1β、MCP-1 mRNA表达水平降低，肺泡结构相对完整，见少许结缔组织增生。 【结论】黄芪甲苷脂质体可以提高甲型流感病毒感染小鼠的生存时间、降低肺组织病毒载量，其机制可能与抑制炎症因子的表达从 而起到抗病毒作用有关。

Objective To observe the therapeutic effect and mechanism of Astragaloside Ⅳ liposomes for influenza A virus infection in mice. Methods Fifty BALB/c mice were randomly divided into normal group （10 mice） and modeling group （40 mice） . The modeling group mice were injected with A/PR/8/34（H1N1） influenza virus liquid via nasal drip. The modeling mice were randomly divided into model group，Oseltamivir group，and Astragaloside Ⅳ Liposomes high- and low- dose groups，with 10 mice in each group. The drug was administered by gavage two hours after infection for five days continuously. The appearance of the mice was observed，the body mass，survival condition and lung index as well as viral load in lung were assessed，pathological feature of lung tissue was observed by hematoxylin-eosin（HE） staining method，and mRNA expression levels of monocyte chemoattractant protein 1 （MCP-1） ，macrophage inflammatory protein 1β（MIP-1β） ，and interferon γ（IFN-γ） ，CXC chemokine ligand 1 （CXCL-1），interleukin （IL）-6，and IL-1β in lung tissues were detected by quantitative polymerase chain reaction（qPCR） method. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the contents of granulocyte-macrophage colony-stimulating factor（GM-CSF） and regulated on activation normal T-cell expressed and secreted（RANTES）in mouse lung tissue. Results Compared with the normal group，mice in the model group showed significant decrease of body mass，shortened survival time（P＜0.001），significantly increased lung index （P＜0.001） ，significantly increased viral load in lung （P＜0.001） ，and significantly increased mRNA expression levels of MIP-1β，IFN- γ，CXCL-1，IL-6，IL-1β and MCP-1 in lung tissue（P＜0.05 or P＜0.001） ，and the structure destruction of lung tissue could be seen in pathology. Compared with the model group，mice in the Astragaloside Ⅳ liposomes high-dose group showed that the decrease in body mass was slowed down，the survival time and survival rate were higher （P＜0.05），and the lung index was significantly decreased （P＜0.05），the viral load in lung was decreased（P＜0.001） and the mRNA expression levels of MIP-1β，IFN-γ，CXCL-1，IL-6，IL-1β and MCP-1 in lung tissue were decreased，and the alveolar structure was relatively intact，and a little connective tissue hyperplasia was seen. Conclusion Astragaloside Ⅳ liposomes can improve the survival time and reduce the viral load of lung tissue in mice with influenza A virus infection，and its mechanism may be related to the inhibition of the expression of inflammatory factors，thus playing an antiviral role.

R285.5

国家中医药管理局中医药防治传染病重点研究室建设项目 （编号：440100000）