摘要
目的研究调节性T细胞与Th17细胞的平衡关系及其对大鼠肺纤维化的影响。方法 SD大鼠10只,随机分为博来霉素(实验组)5只和生理盐水组5只(对照组),博来霉素组气管内给药复制大鼠肺纤维化动物模型(博来霉素5mg/kg),对照组气管内注射等量生理盐水。第28天处死动物,肺组织病理切片苏木精-伊红染色,免疫组织化学方法检测IL-2、IL-6、IL-17和TGF-β的表达,以IL-17的表达水平作为衡量Th17细胞功能和数量的指标,流式细胞术检测CD4+调节性T细胞和CD8+调节性T细胞的比例。结果博来霉素组肺纤维化明显;与对照组大鼠相比,Ashcroft评分差异有统计学意义。博来霉素组IL-2、IL-6、IL-17和TGF-β的表达水平明显上升,与对照组比较,差异具有统计学意义。总体样本数据行相关分析提示IL-6和IL-17表达水平具有正相关性,IL-17与TGF-β也具有正相关性。CD4+CD25+Foxp3+细胞占CD4+CD25+细胞百分比较对照组没有增高,差异无统计学意义。只有博来霉素组CD8+CD25+Foxp3+细胞占CD8+CD25+细胞百分比较对照组增高,差异具有统计学意义(P<0.05)。结论博来霉素致肺纤维化大鼠中存在Th17细胞和调节性T细胞的数量功能的相对不平衡,这种不平衡可能导致肺纤维化病情进展。这种不平衡可能与影响Th17细胞和调节性T细胞分化的IL-2、IL-6、TGF-β等细胞因子表达水平改变有关。
Objective To study the imbalance between regulatory T cells and Thl7 cells and its effect on pulmonary fibro- sis in rats. Methods The rat model of pulmonary fibrosis was established by intratracheally instilling bleomycin（5 mg/kg）. Control rats were treated by intratracheal instillation of normal saline equal volume. On the 28th day, all rats were sacrificed and the peripheral blood and the lung tissues were harvested. The severity of pulmonary fibrosis was assessed by Ashcroft sco- ring. The lung tissues were immunohistochemically stained to detect the expression of IL-6, IL-17, TGF-13 and IL-2. Flow cytom- etry was used to detect the percentage of CD8＋ CD25＋ Foxp3＋ T cells and CD4＋ CD25＋ Foxp3＋ T cells. Results The pulmonary fibrosis in the bleomycin group was more obvious than in control group. There was a significant difference in the Ashcroft score between the two groups（P〈0.01）. The expression levels of IL-6,IL-17,TGF-13 and IL-2 are increased in the bleomycin group compared with the control group. Correlation analysis suggested a positive correlation between IL-6 and IL-17 expression lev- els. And the expression level of IL-17 was positively correlated with TGF-13. The percentage of CD4＋ CD25＋ Foxp3＋ T cells in CD4＋ CD25＋ T cells of the bleomycin group was not significantly increased as compared with that in the control group. The per- centage of CD8＋ CD25＋ Foxp3＋T cells in CD8＋ CD25--T cells in the bleomycin group was significantly higher than that in the control group（P〈0.05） . Conclusion The development of pulmonary fibrosis may be related to the imbalance between regula- tory T cells and Thl7 cells. IL-2, IL-6,and TGF-13 can influence the differentiation of Th17 cells and regulatory T cells. The im- balance between the regulatory T cells and Thl7 cells may be related to changes of these cytokines.
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2013年第2期161-166,共6页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金
武汉市科技攻关计划资助项目(No.200751099415)
