中文摘要：

探讨阻断IL-17A对小鼠肺损伤后肺纤维化发生的预防作用及其机制。博来霉素造成小鼠肺损伤7天后给予抗IL-17A中和性抗体治疗,第14天取材。利用HE和天狼星红染色法观察肺组织炎症及胶原沉积情况;利用生化检测试剂盒检测肺组织中羟脯氨酸及肺泡灌洗液中胶原含量;利用Kaplan-Meier法统计小鼠生存率;利用ELISA方法检测肺泡灌洗液中IL-17A、TGF-β1、IL-13、IFN-γ表达水平;利用免疫印迹分析方法检测肺组织中p65NF-κB、p50NF-κB、COX-2、5-LOX、15-LOX的表达或活化。结果显示：与模型对照组比较,阻断IL-17A能够降低胶原沉积、减少羟脯氨酸及胶原含量、提高小鼠生存率,并能抑制炎症反应,降低IL-17A、TGF-β1、IL-13,升高IFN-γ、COX-2、5-LOX、15-LOX表达水平,抑制p65NF-κB活化但促进p50NF-κB活化。结果提示,阻断IL-17A能预防肺损伤后肺纤维化发生,其机制与促进p50NF-κB活化及其下游分子表达、抑制急性炎症转变为慢性炎症反应有关。

英文摘要：

This study is to determine the preventive effect and mechanism of targeting IL-17A on pulmonary inflammation and fibrosis after acute lung injury.Mice were treated with anti-IL-17A antibody on the day 7 and sacrificed on the day 14 after bleomycin lung injury.The pulmonary inflammatory status and the deposition of collagen were measured by HE and Sirius stains staining.The contents of hydroxyproline and collagen were measured by using commercial kits.The survival rate of mice was calculated by Kaplan-Meier methods.The inflammatory cytokines in bronchoalveolar lavage fluid were measured by ELISA and the expressions of inflammation-related molecules were detected by Western blotting assay.Targeting of IL-17A could prevent the development of lung inflammation,decrease collagen deposition and the contents of hydroxyproline,and protect against the development of pulmonary fibrosis,which together led to an increase in the animal survival.Moreover,blocking IL-17A decreased the expression of pro-fibrotic cytokines such as IL-17A,TGF-β1 and IL-13;increased the expression of anti-fibrotic or anti-inflammatory factors such as IFN-γ,COX-2,5-LOX,15-LOX.Indeed,IL-17A antagonism suppressed the activation of pro-inflammatory p65NF-κB but enhanced the activation of pro-resolving p50NF-κB.In conclusion,that blockade of IL-17A prevents the development of pulmonary fibrosis from acute lung injury,is because blocking IL-17A may prevent acute inflammation converting to chronic inflammation.