IL-35、Th17/Treg细胞失衡在大鼠肺纤维化中的表达及意义

摘要

目的 研究IL-35、Th17/Treg失衡在大鼠肺纤维化中的表达及意义.方法 随机将60只健康雌雄各半Wistar大鼠分为两组:对照组30只(生理盐水组)、肺纤维化组30只(博来霉素组),分别于实验第7天、第14天、第28天处死对照组、模型组各10只大鼠,留取各组大鼠肺组织、肺泡灌洗液,观察大鼠肺组织形态病理学变化(HE染色和Masson三色染色);测定支气管冲洗液及肺组织中Treg、Th17细胞,IL-35、IL-17表达水平,并分析IL-35与Th17/Treg的相互关系.结果 1.肺纤维化组与对照组相比,肺组织炎症程度、肺纤维化程度显著,肺部炎症以造模第7d最明显.2.两组相比,肺纤维化组IL-35、Treg细胞表达水平显著低于对照组,IL-17、Th17细胞表达显著高于对照组,差异均具有统计学意义.3.肺纤维化组IL-35与IL-17表达水平呈明显的负相关(r= -0.378,P<0.01),IL-35与Treg细胞表达水平呈正相关(r=0.461,P<0.01),IL-35与Th17/Treg细胞表达水平呈负相关(r= -0.386,P<0.01).结论 本研究通过对大鼠肺纤维化组、对照组IL-35、IL-17、Th17/Treg细胞表达水平与相关性分析;提示IL-35可能参与肺纤维化Th17/Treg细胞平衡的调节,对IL-35的调控有可能成为肺纤维化治疗的新的靶点.%Objective To study the expression and significance of IL-35,Th17/Treg imbalance in rats with pulmonary fibrosis. Methods A total of 60 healthy male and female Wistar rats were randomly divided into two groups:30 rats in the control group(the normal saline group),and 30 rats in the pulmonary fibrosis group(the bleo-mycin group). Every 10 rats in the control group and the model group were sacrificed on the 7th day, the 14th day and the 28th day respectively. The lung tissue and alveolar lavage fluid were collected from each group to observe the morphological changes of lung tissue by HE staining and Masson trichrome staining. The levels of Treg,Th17 cells, IL-35 and IL-17 were detected in bronchial rinse and lung tissue. The relationship between IL-35 and Th17/Treg was analyzed. Results 1. Compared with the control group, the inflammation and pulmonary fibrosis degree was more significant in the pulmonary fibrosis group,and the inflammation of the lungs was the most pronounced at the 7th day. 2. The expression of IL-35 and Treg cells in the pulmonary fibrosis group was significantly lower than that in the con-trol group. The expression of IL-17 and Th17 cells was significantly higher than that of the control group. 3. There was a significant negative correlation between IL-35 and IL-17 expression in the pulmonary fibrosis group (r= -0. 378,P<0.01),IL-35 was positively correlated with Treg cell expression (r=0.461, P<0.01), and IL-35 was negatively correlated with Th17 / Treg cell expression (r= -0.386,P<0.01). Conclusion The research on the expression and relativity of IL-35, IL-17 and Th17/Treg cells in rat pulmonary fibrosis group and control group re-veals that IL-35 may be involved in the regulation of Th17/Treg cell balance in lung fibrosis,and the regulation of IL-35 may be a new target for the treatment of pulmonary fibrosis.