【摘要】 目的:研究T辅助细胞17(Th17)及相关细胞因子在系统性硬化病(systemic sclerosis,SSc)小鼠模型外周血、皮肤、肺部的表达及意义。方法:20只雌性BALB/c小鼠随机分为对照组和博莱霉素注射4周组(SSc组),观察小鼠皮肤/肺部炎症和纤维化(pulmonary fibrosis,PF)的病理切片,流式细胞计数检测外周血、皮肤/肺组织CD4+IL-17+Th17细胞,荧光定量PCR检测小鼠皮肤/肺部维甲酸相关孤独受体(RORγt)、IL-17A和IL-6 mRNA的表达,酶联免疫吸附试验检测血清IL-17、IL-6水平,并分析这些指标的相关性。结果:SSc组比对照组皮肤炎症和肺纤维化评分(Ashcroft评分)明显增加(2.6±0.84 vs.0.4±0.52,2.80±1.81 vs.0.60±0.70),皮肤/肺羟脯氨酸(hydroxyproline,HYP)的含量明显增多[(3.17±1.74)mg/g vs.(1.45±0.40)mg/g,(0.53±0.14)mg/g vs.(0.38±0.16)mg/g],均P<0.05。SSc组外周血、皮肤和肺组织Th17细胞比例较对照组明显增加[(2.07±0.89)%vs.(1.02±0.32)%,(5.80±2.02)%vs.(1.64±0.58)%,(5.24±2.43)%vs.(1.92±0.98)%,P<0.01];与对照组相比,SSc组皮肤/肺组织IL-17A、IL-6 mRNA的表达量,皮肤RORγt mRNA的表达量增高,均P<0.05。SSc组外周血IL-17、IL-6含量明显增高(P<0.01)。外周血Th17细胞、IL-17和IL-6的含量与皮肤/肺部炎症、PF评分、皮肤HYP含量呈密切正相关,皮肤/肺组织Th17细胞分别与皮肤/肺部炎症、皮肤/肺HYP含量密切正相关。结论:Th17细胞在SSc小鼠模型外周血、皮肤及肺组织表达增高,与皮肤/肺部炎症、纤维化病变密切正相关,并通过IL-17、IL-6等细胞因子参与SSc的发病。更多还原

【Abstract】 Objective:To study the expression and significance of Th17 cells and related cytokines in the peripheral blood,skin and lung in a murine model of systemic sclerosis(SSc).Methods: Twenty female BALB/c mice were randomly divided into 2 groups,including a control group and a bleomycin(BLM)-injected-4-week group(SSc group).Pathological changes of the skin and lung were detected.The proportion of CD4+IL-17+Th17 cells in the peripheral blood,skin and lung of the mice was determined by flow cytometry.The mRNA expressions of RORγt,IL-17A,and IL-6 of the skin and lung were evaluated by real-time PCR.Enzyme linked immunosorbent assay was used to measure the levels of IL-17 and IL-6 in the serum.Results: Dermal inflammation and the score of PF were significantly increased in the SSc group as compared with the control group(2.60±0.84 vs.0.40±0.52,2.80±1.81 vs.0.60±0.70).Hydroxyproline(HYP) contents of the skin and lung were obviously increased in the SSc group than in the control group [(3.17±1.74) mg/g vs.(1.45±0.40) mg/g,(0.53±0.14) mg/g vs.(0.38±0.16) mg/g],all P<0.05.The percentage of Th17 cells in the peripheral blood,skin and lung of the SSc group were significantly increased as compared with the control group [(2.07±0.89)% vs.(1.02±0.32)%,(5.80±2.02)% vs.(1.64±0.58)%,(5.24±2.43)% vs.(1.92±0.98)%,P <0.01].Compared with the control group,the mRNA levels of IL-17A,RORγt,IL-6 in the skin and lung of the SSc group were higher.The levels of IL-17,IL-6 of the SSc group in the serum were significantly increased,all P<0.05.The frequency of Th17 cells,and the levels of IL-17 and IL-6 in the blood had a positive correlation with dermal and pulmonary inflammation,fibrosis and HYP contents of the skin and lung,The frequency of Th17,IL-17and IL-6 in the skin and lung had,respectively,a positive correlation with dermal and pulmonary inflammation,HYP contents of the skin and lung,all P<0.01.Conclusion: Th17 cells were significantly increased in the peripheral blood,skin and lung of a murine model of SSc,and had an intimate relationship with inflammation and fibrosis of the skin and lung,and involved the pathogenesis of SSc through producing IL-17,IL-6.更多还原