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。
Action Mechanism of Il-12 in Airway Remodeling in Mice with RSV Infection
To explore the action mechanism of interleukin 12(IL-12)in airway remodeling in mice with Respiratory syncytial virus(RSV)infection,the type Ⅱ alveolar epithelial cells(AEC Ⅱ)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 and α-SMA in mice with IL-12 P40(-/-)were higher than those in control mice while macrophages,levels of IL-12,IFN-γ and 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.
Respiratory syncytial virusinterleukin 12airway inflammationsignal transducer and activator of transcription 4airway remodeling
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