Th17细胞在肺纤维化小鼠中的动态变化及作用机制

Dynamic change of Th17 cells in bleomycin-induced pulmonary fibrosis

目的:研究Th17细胞在博来霉素致肺纤维化小鼠中的动态变化及作用机制.方法:小鼠随机分为对照组、博来霉素组和全反式维甲酸组.博来霉素组和维甲酸组利用博来霉素建立小鼠肺纤维化模型,维甲酸组在造模第0天每只腹腔注射全反式维甲酸.评价小鼠肺组织病理形态变化;检测肺组织中羟脯氨酸含量和维甲酸相关孤儿受体(RORγt) mRNA的表达;应用流式细胞术分析脾中Th1、Th2、Th17细胞的动态变化.结果:博来霉素组和维甲酸组羟脯氨酸(HYP)含量逐渐升高,博来霉素组第7、14、28天高于对照组和维甲酸组,第28天时达最高;博来霉素组、维甲酸组在4个时间点与对照组比较,Th17、Th2细胞均明显增高,Th1细胞低于对照组,RORγt mRNA表达水平上调.其中维甲酸组Th17、Th2细胞及RORγt mRNA表达水平低于博来霉素组,Th1细胞高于博来霉素组.结论:Th17细胞可能参与特发性肺纤维化的发病机制,并通过调节Th1、Th2细胞分化来发挥作用.

Objective:To investigate the dynamic change of Th17 cells in a bleomycin(BLM)-induced pulmonary fibrosis model.Methods:sixty mice were randomly divided into 3 groups:control group,model group and all-trans retinoic acid(ATRA) group.BLM and ATRA groups were established by intratracheal injection of bleomycin.The mice of ATRA group were injected into abdominal cavity with ATRA after receiving intratracheal instillation of BLM on day 0.They should be injected 3 times a week.Mice were sacrificed at the 3rd,7th,14 th,28th day after modeling.Lung tissues were restored to analyze the pathological changes,determine the levels of hydroxyproline(HYP) and measure the mRNA expression of RORyt by real-time PCR.Proportion of Th1,Th2 and Th17 cells in the spleen was evaluated by flow cytometry.Results:In BLM and ATRA groups,the level of HYP was higher on the 7th,14 th,28th day than A group,which reached the peak on the28 th day.The level of HYP in BLM group was higher than ATRA group.The proportions of Th17 and Th2 cells were higher in BLM and ATRA groups than control group,but the proportion of Thl cells was lower.The mRNA expression level of RORyt was up-regulated in BLM and ATRA groups.Between BLM and ATRA group,the mRNA expression level of RORyt,the proportion of Th17 and Th2 cells in group ATRA were lower but Thl cells were higher.Conclusion:Th17 cells are associated with idiopathic pulmonary fibrosis,which may be involved in the pathogenesis of idiopathic pulmonary fibrosis by regulating Thl and Th2 cells.