IL-12在RSV感染小鼠气道重塑中的作用机制分析  

Action Mechanism of Il-12 in Airway Remodeling in Mice with RSV Infection

作　　者：陶双 董善武 TAO Shuang;DONG Shanwu(Department of Pediatrics,Wuhan Fourth Hospital,Wuhan 430033,China)

机构地区：[1]武汉市第四医院儿科,武汉430033

出　　处：《中国动物传染病学报》2024年第4期11-16,共6页Chinese Journal of Animal Infectious Diseases

基　　金：湖北省卫生健康委员会2019~2020年度面上项目(WJ2019M020)。

摘　　要：为探究白细胞介素12(interleukin 12,IL-12)在呼吸道合胞病毒(Respiratory syncytial virus,RSV)感染小鼠气道重塑中的作用机制。体外培养大鼠肺泡Ⅱ型上皮细胞(AECⅡ),经RSV感染后观测细胞中IL-12表达的释放规律。采用滴鼻法建立RSV感染模型,观察IL-12 P40基因敲除[IL-12 P40(-/-)]小鼠肺组织病理改变、BALF中Th1/Th2细胞因子、肺组织信号转导和转录激活因子4(signal transducer and activator of transcriptional,STAT4)及气道重塑标记物表达的变化。感染3、12、24 h,感染组IL-12水平均低于对照组(P<0.05)。IL-12 P40(-/-)小鼠淋巴细胞、中性粒细胞、嗜酸性粒细胞数、IL-5、IL-13、气道炎症病理评分、ColⅠ、FN-1和α-SMA表达水平高于野生型,巨噬细胞数、IL-12、IFN-γ和p-STAT4/STAT4水平低于野生型(P<0.05)。RSV感染诱导AECⅡ细胞和野生型小鼠IL-12水平下调,IL-12缺乏可加重RSV小鼠气道炎症和气道重塑,可能与抑制STAT4活化有关。To explore the action mechanism of interleukin 12(IL-12)in airway remodeling in mice with Respiratory syncytial virus(RSV)infection,the typeⅡalveolar epithelial cells(AECⅡ)of rats were cultured in vitro and the release rules of IL-12 in the cells were observed after RSV inoculation.The RSV infection model was developed in mice with IL-12 P40 gene knockout[IL-12 P40(-/-)]by nasal drip method.The infected mice were examined for pathological changes of lung tissues,Th1/Th2 cytokine levels in bronchoalveolar lavage fluid(BALF),signal transducer and activator of transcription 4(STAT4)and airway remodeling markers in lung tissues.At 3,12 and 24 h after infection,IL-12 level in infection group was lower than that in control group(P<0.05).The lymphocytes,neutrophils and eosinophils,IL-5,IL-13,pathological scores of airway inflammation,and expression levels of ColI,FN-1 andα-SMA in mice with IL-12 P40(-/-)were higher than those in control mice while macrophages,levels of IL-12,IFN-γand p-STAT4/STAT4 were lower than those in control mice(P<0.05).These results showed that RSV infection induced the down-regulation of IL-12 level in AEC II and control mice.IL-12 deficiency would aggravate airway inflammation and airway remodeling in RSV mice,which might be related to inhibiting STAT4 activation.

关 键 词：呼吸道合胞病毒 白细胞介素12 气道炎症 转录激活因子4 气道重塑 

分 类 号：R725.6[医药卫生—儿科] R-332[医药卫生—临床医学]