【摘要】 目的:探讨胶原诱导性关节炎(CIA)关节滑膜Treg/Th17平衡状态以及TNF-α拮抗剂TNFR-Fc对Treg/Th17的影响。方法:建立CIA模型,观察踝关节组织病理变化,ELISA检测血浆肿瘤坏死因子α(TNF-α),免疫荧光双标法检测关节滑膜Treg/Th17的表达。结果:CIA组TNF-α较正常对照组及TNFR-Fc治疗组显著升高(P<0.01),TNFR-Fc治疗组与正常对照组间差异无统计学意义(P>0.05);CIA组滑膜组织的CD4+Foxp3+Treg/CD4+细胞比例与正常对照组比较无明显差异(23.12%±4.93%vs 24.66%±5.82%,P>0.05),而TNFR-Fc治疗组则升高明显(33.07%±5.14%);CIA组CD4+RORγt+Th17/CD4+细胞比例显著增高(9.74%±2.23%vs正常对照组1.00%±0.59%,TNFR-Fc治疗组5.63%±1.76%,P<0.01)。结论:CIA大鼠关节滑膜存在Treg/Th17分化失衡;TNFR-Fc可能通过抑制关节滑膜Th17细胞分化,诱导Treg细胞生成/聚集,使得病变关节的Treg/Th17平衡得以恢复。更多还原

【Abstract】 AIM: To investigate the balance of Treg/Th17 in synovium of collagen-induced arthritis(CIA) and the impact of tumor necrosis factor α(TNF-α) blockage therapy.METHODS: Rat CIA model was established by bovine II collagen injection.The pathological score was evaluated by HE staining and toluidine blue staining.The TNF-α level in plasma was measured by ELISA.The expression of Treg/Th17 in synovium was detected by double staining immunofluorescence.RESULTS: The plasma level of TNF-α in CIA group was significantly higher than that in control group and TNFR-Fc treatment group(P<0.01),whereas no significant difference was found between TNFR-Fc treatment group and control group(P>0.05).No significant difference between CIA group and control group in the ratio of CD4+Foxp3+Treg cells/CD4+ cells in synovium(23.12%±4.93% vs 24.66%±5.82%,P>0.05) was observed,whereas the ratio in TNFR-Fc treatment group was significantly increased(33.07%±5.14%).The ratio of CD4+RORγt+Th17 cells/CD4+ cells in CIA group was significantly higher than that in control group and TNFR-Fc treatment group(9.74%±2.23% vs 1.00%±0.59%,5.63%±1.76%,P<0.01).CONCLUSION: Differentiation disturbance of Treg/Th17 exists in the synovium of CIA rats.TNFR-Fc may restore the balance of Treg/Th17 by inhibiting Th17 cell differentiation and inducing the production or accumulation of Treg.更多还原