免疫抑制剂环磷酰胺对流感病毒性肺炎小鼠模型“肺外传变”的影响  

Effects of immunosuppressant cyclophosphamide on"extrapulmonary trans-mission"in mouse model of influenza virus pneumonia

作　　者：赵澄 张香港 王小奇 胡珏 刘畅 卢芳国 ZHAO Cheng;ZHANG Xianggang;WANG Xiaoqi;HU Jue;LIU Chang;LU Fangguo(School of Integrated Chinese and Western Medicine,Hunan University of Chinese Medicine,Changsha 410208,China;School of Medicine,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学中西医结合学院,长沙410208 [2]湖南中医药大学医学院,长沙410208

出　　处：《中国免疫学杂志》2025年第2期418-423,432,共7页Chinese Journal of Immunology

基　　金：国家自然科学基金(82074250,82374266);湖南省自然科学基金(2020JJ4063);湖南中医药大学一流学科《基础医学》资助项目(1);湖南中医药大学中西医结合病原生物学湖南省重点实验室开放项目(2022KFJJ01);湖南省研究生科研创新项目(CX20220783);中西医结合学院-明康中锦联合基金(2022MKZJ01)。

摘　　要：目的:观察免疫抑制剂环磷酰胺对流感病毒性肺炎小鼠模型“肺外传变”的影响。方法:BALB/c小鼠随机分为正常组、病毒组、环磷酰胺组、病毒+环磷酰胺组。环磷酰胺组和病毒+环磷酰胺组腹腔注射环磷酰胺1次,24 h后,病毒组和病毒+环磷酰胺组滴鼻流感病毒建立流感病毒感染模型。滴鼻后3 d、5 d、7 d,常规法测算肺指数、心指数、肝指数、脾指数、肾指数;HE染色观察肺组织、心组织、肝组织、脾组织、肾组织病理变化;ELISA检测血清炎症细胞因子IL-1β、IL-6、TNF-α水平;RT-qPCR检测各组织流感病毒载量和炎症因子IL-1β、IL-6、TNF-α表达。结果:与正常组和病毒组比较,病毒+环磷酰胺组小鼠肺指数、心指数显著升高(P<0.05或P<0.01);脾指数显著降低(P<0.05或P<0.01);肺组织、心组织、肝组织、脾组织出现不同程度病理损伤;血清炎症因子IL-6水平显著升高(P<0.05或P<0.01);肺组织、心组织、肝组织、脾组织和肾组织IAV NP mRNA水平显著升高(P<0.05或P<0.01);肺组织和心组织IL-1β、IL-6、TNF-α mRNA水平显著升高(P<0.05或P<0.01)。结论:免疫抑制剂环磷酰胺可导致流感病毒性肺炎小鼠模型肺外组织器官损伤,以心脏损伤最为严重。环磷酰胺有利于建立流感病毒性肺炎“肺外传变”模型。Objective:To observe effect of immunosuppressant cyclophosphamide on"extrapulmonary transmission"of mouse model of influenza virus pneumonia.Methods:BALB/c mice were randomly divided into normal group,virus group,cyclophospha‐mide group,virus+cyclophosphamide group.Cyclophosphamide group and virus+cyclophosphamide group were intraperitoneally injected with cyclophosphamide once,24 h afterwards,virus group and virus+cyclophosphamide group were administered nasal influ‐enza virus to establish influenza virus infection model,and 3,5,7 days after nasal instillation,lung index,heart index,liver index,spleen index and kidney index were measured by conventional methods;pathological changes of lung tissue,heart tissue,liver tissue,spleen tissue and kidney tissue were observed by HE staining;ELISA was used to detect levels of serum inflammatory cytokines IL-1β,IL-6,TNF-α;RT-qPCR was used to detect influenza virus load and expressions of inflammatory factors IL-1β,IL-6,TNF-αin each tissue.Results:Compared with normal group and virus group,lung index and heart index of mice in virus+cyclophosphamide group were significantly increased(P<0.05 or P<0.01);spleen index was significantly decreased(P<0.05 or P<0.01);lung tissue,heart tissue,liver tissue and spleen tissue showed different degrees of pathological damage;serum inflammatory factor IL-6 level was increased significantly(P<0.05 or P<0.01);lung tissue,heart tissue,liver tissue,spleen tissue and mRNA levels of IAV NP in kidney tissue were significantly increased(P<0.05 or P<0.01);mRNA levels of IL-1β,IL-6 and TNF-αin lung and heart tissues were significantly increased(P<0.05 or P<0.01).Conclusion:Immunosuppressant cyclophosphamide can cause damage to extrapulmonary tissues and organs in a mouse model of influenza virus pneumonia,among which heart damage is the most serious.Cyclophosphamide is beneficial to establish model of"extrapulmonary transmission"of influenza virus pneumonia.

关 键 词：免疫抑制 环磷酰胺 流感病毒性肺炎 肺外传变 

分 类 号：R511.7[医药卫生—内科学] R392[医药卫生—临床医学]