阿维A通过下调Th17细胞相关因子改善硬皮病小鼠模型皮肤及肺组织纤维化程度

发布时间：2018-01-12 11:42

本文关键词：阿维A通过下调Th17细胞相关因子改善硬皮病小鼠模型皮肤及肺组织纤维化程度　出处：《中国皮肤性病学杂志》2017年04期 　论文类型：期刊论文

【摘要】：目的通过对系统性硬皮病(systemic scleroderma,SSc)小鼠模型外周血、皮肤和肺部Th17和Treg细胞及相关细胞因子表达的检测,探讨阿维A治疗SSc小鼠皮肤和肺纤维化病变可能的作用机制。方法 32只BALB/c小鼠随机均分为PBS对照组、博来霉素模型组、阿维A低剂量(6mg/kg)组和高剂量(12mg/kg)组,给药4周后处死。观察小鼠皮肤及肺部炎症和纤维化的病理切片,流式细胞仪检测外周血中Th17和Treg在CD4~+T细胞比例,通过ELISA检测小鼠血清IL-17A,IL-10,IL-6,TGF-β1的水平,RT-PCR检测皮肤和肺组织中IL-17A,RORγT,IL-6,TGF-β1,Fox P3 mRNA的表达,并分析这些结果的相关性。结果与模型组相比,高/低浓度阿维A组小鼠皮肤厚度和炎症评分均有明显的下降(P0.01),肺部的纤维化评分和炎症评分也有显著降低(P0.05)。流式细胞仪检测发现,经阿维A干预的两组小鼠外周血中Th17细胞比例都有显著增加(P0.01),而Treg细胞比例的变化差异无统计学意义(P0.05)。ELISA检测发现,与模型组比较,治疗组小鼠外周血中IL-17A,TGF-β1,IL-6水平均有显著下降(P0.05),而IL-10的表达均未发生明显变化(P0.05)。RT-PCR检测发现,治疗组皮肤和肺组织中Th17细胞相关因子IL-17A,RORγT,IL-6,TGF-β1表达水平显著下降(P0.05),而皮肤和肺组织中Treg相关的Fox P3 Treg mRNA表达在阿维A干预前后没有明显变化(P0.05)。结论阿维A能够通过降低Th17相关细胞因子的水平,减轻免疫炎症反应,改善硬皮病小鼠皮肤和肺组织纤维化的程度。
[Abstract]:Objective to study the peripheral blood of systemic scleroderma systemic scleroderma (SSC) mouse model. The expression of Th17 and Treg cells and related cytokines in skin and lung were detected. To explore the possible mechanism of Avera in treating skin and pulmonary fibrosis in SSc mice. Methods 32 BALB/c mice were randomly divided into PBS control group and bleomycin model group. The mice were killed 4 weeks later in the low dose of avea 6 mg / kg group and the high dose group of 12 mg / kg group. The pathological sections of inflammation and fibrosis in the skin and lung were observed. The ratio of Th17 and Treg in CD4 ~ T cells was detected by flow cytometry, and the IL-10 IL-6 in serum of mice was detected by ELISA. The level of TGF- 尾 1 was measured by RT-PCR to detect the expression of IL-17AfROR 纬 -Tf6TGF- 尾 1FCPP3 mRNA in skin and lung tissues. Results compared with the model group, the skin thickness and inflammation score of the high / low concentration Avera group decreased significantly (P 0.01). Pulmonary fibrosis score and inflammation score also decreased significantly (P 0.05). The percentage of Th17 cells in peripheral blood of the two groups treated with Avera increased significantly (P 0.01). However, there was no significant difference in the proportion of Treg cells between the two groups. The results of Elisa showed that IL-17A- TGF- 尾 1 in peripheral blood of the treatment group was higher than that of the model group. The level of IL-6 decreased significantly (P 0.05), but the expression of IL-10 did not change significantly. In the treatment group, the expression level of IL-17AnROR 纬 -Tf6 TGF- 尾 1 in the skin and lung tissues decreased significantly (P 0.05). However, the expression of Fox P3 Treg mRNA related to Treg in skin and lung tissues did not change significantly before and after Avera intervention (P 0.05). Conclusion Avera can reduce the level of cytokines associated with Th17. Reduce immune inflammation and improve the degree of skin and lung fibrosis in scleroderma mice.
【作者单位】：首都医科大学附属北京世纪坛医院皮肤科;中国医学科学院中国协和医科大学北京协和医院风湿免疫科;中国藏学研究中心北京藏医院;
【基金】：北京市自然科学基金资助项目(7153168) 首都医科大学附属北京世纪坛医院中青年学科骨干培养专项(2016-QB06)
【分类号】：R-332;R593.25
【正文快照】： 系统性硬化症(systemic sclerosis,SSc)即硬皮病是以自身免疫性结缔组织病变,累及皮肤和内脏器官纤维化、微血管系统异常、免疫功能异常的病理三联征为主要特点的疾病[1]。相应的治疗原则也是根据病理表现对症治疗,使用抗纤维化药物、抗炎免疫抑制剂、血管活性药物以及其他创

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