摘要
目的:观察佐剂关节炎(Adjuvant arthritis,AA)大鼠肺功能降低与辅助T细胞(Th)、调节T细胞(Treg)及Foxp3的关系。方法:将SD大鼠随机分为正常对照(NC)组和模型对照(MC)组,每组15只,向MC组大鼠右后足跖皮内注射弗氏完全佐剂0.1 ml致炎,复制成AA模型。致炎48 d后,采用小动物肺功能仪检测肺功能,酶联免疫吸附法检测内皮素(ET)-1、白细胞介素(IL)-10、γ干扰素(IFN-γ),免疫组化法检测肺组织IL-1β、IL-10表达,流式细胞仪测定Treg的表达,采用PCR与免疫印迹检测肺组织Foxp3表达。结果:与NC组相比,MC组大鼠IFN-γ、ET-1、IL-1β升高;肺功能参数50%肺活量的最大呼气流量(FEF50)、75%肺活量的最大呼气流量(FEF75)、最大呼气中期流量(MMF)、用力最大呼气流量(PEF)降低,IL-10、CD4+CD25+Foxp3+Treg、Foxp3表达降低(P<0.05或P<0.01);相关分析显示,AA大鼠肺功能参数FEF75、MMF分别与IFN-γ、Th1/Th2、IL-1β呈负相关,FEF50、PEF与ET-1呈负相关;PEF、FEF75分别与IL-10、Foxp3 mRNA、Foxp3蛋白呈正相关,FEF75与CD4+CD25+Foxp3+Treg呈正相关(P<0.05或P<0.01)。结论:AA大鼠肺功能下降可能是佐剂致炎后Th细胞分泌紊乱、细胞因子失衡、内皮细胞增多,使肺组织Foxp3表达抑制,进而CD4+CD25-T细胞转化成CD4+CD25+Treg受阻,最终导致RA肺功能降低。
Objective ：To observe the relationship of pulmonary function, regnlatory T cells （Treg） and Foxp3 in adjuvant-in- duced arthritis in rats. Methods： SD rats were randomly divided into normal control （NC） group and model control （MC） group even- ly. The MC group were intracutaneously injected with 0.1 ml of Freund＇ s complete adjuvant in the fight hindlimb. Forty-eight days after proinflammatory, pulmonary function was detected by spirometer, endothelial prime （ET）-1, interleukin hormone （IL）-10, gamma interferon （IFN-γ） were measured by enzyme-linked immunosorbent assay, IL-1β, IL-10 in lung tissue were detected by immunohistochemistry, Treg was measured by flow eytometry, and FoxP3 mRNA, Foxp3 protein were detected by PCR, Western blot, accordingly. Results： Compared with the NC group, the levels of IFN-γ, ET-1, IL-1β were increased, and parameters of pulmonary function such as 50% of forced expiratory flow （ FEF50 ）, 75% of forced expiratory flow （ FEFTs ）, maximum mid-expiratory flow （ MMF）, peak expiratory flow （PE17） were reduced in the MC group, while the expression of IL-IO, CD4＋ CD25 ＋ Foxp3 ＋ Treg, Foxp3 in the NC group were significantly lower than that of the MC group （ P 〈 O. 05 or P 〈 0.01 ）. The correlation analysis showed that the negative correlation between FEF75, MMF and IFN-γ, Th1/Th2, IL-113, the negative correlation between FEFs0, PEF and ET-1. The positive correlation between PEF, FEF75 and Foxp3, FEF75 and IL-10, CD4 ＋ CD25 ＋ Foxp3 ＋ Treg （ P 〈 0.05 or P 〈 0.01 ）. Conclusion： The decline in the pulmonary function may be cause by the turbulence of excretion of Th cell after inflammatory, imbalance of cytokine, and oversecretion of the endothelial cell. The expression of Foxp3 was suppress in lung tissue. The status was obstructed which transforming CD4 ＋ CD25 - T cell into CD4 ＋ CD25 ＋ Treg, and leading to reduce in pulmonary function lung of RA.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2014年第1期93-99,共7页
Chinese Journal of Immunology
基金
国家自然科学基金(No.81173211)
国家中医药重点学科中医痹病学建设项目(国中医药发[2009]30号)
安徽省科技厅科研计划项目(09020304046)
安徽省卫生厅中医药科研项目(2009ZY05)
安徽中医学院科技创新团队项目(2010TD005)
