本文關(guān)鍵詞：阿維A通過下調(diào)Th17細(xì)胞相關(guān)因子改善硬皮病小鼠模型皮膚及肺組織纖維化程度　出處：《中國皮膚性病學(xué)雜志》2017年04期 　論文類型：期刊論文

  更多相關(guān)文章： 硬皮病 阿維A T輔助細(xì)胞 調(diào)節(jié)性T細(xì)胞 小鼠模型

【摘要】：目的通過對系統(tǒng)性硬皮病(systemic scleroderma,SSc)小鼠模型外周血、皮膚和肺部Th17和Treg細(xì)胞及相關(guān)細(xì)胞因子表達(dá)的檢測,探討阿維A治療SSc小鼠皮膚和肺纖維化病變可能的作用機(jī)制。方法 32只BALB/c小鼠隨機(jī)均分為PBS對照組、博來霉素模型組、阿維A低劑量(6mg/kg)組和高劑量(12mg/kg)組,給藥4周后處死。觀察小鼠皮膚及肺部炎癥和纖維化的病理切片,流式細(xì)胞儀檢測外周血中Th17和Treg在CD4~+T細(xì)胞比例,通過ELISA檢測小鼠血清IL-17A,IL-10,IL-6,TGF-β1的水平,RT-PCR檢測皮膚和肺組織中IL-17A,RORγT,IL-6,TGF-β1,Fox P3 mRNA的表達(dá),并分析這些結(jié)果的相關(guān)性。結(jié)果與模型組相比,高/低濃度阿維A組小鼠皮膚厚度和炎癥評分均有明顯的下降(P0.01),肺部的纖維化評分和炎癥評分也有顯著降低(P0.05)。流式細(xì)胞儀檢測發(fā)現(xiàn),經(jīng)阿維A干預(yù)的兩組小鼠外周血中Th17細(xì)胞比例都有顯著增加(P0.01),而Treg細(xì)胞比例的變化差異無統(tǒng)計學(xué)意義(P0.05)。ELISA檢測發(fā)現(xiàn),與模型組比較,治療組小鼠外周血中IL-17A,TGF-β1,IL-6水平均有顯著下降(P0.05),而IL-10的表達(dá)均未發(fā)生明顯變化(P0.05)。RT-PCR檢測發(fā)現(xiàn),治療組皮膚和肺組織中Th17細(xì)胞相關(guān)因子IL-17A,RORγT,IL-6,TGF-β1表達(dá)水平顯著下降(P0.05),而皮膚和肺組織中Treg相關(guān)的Fox P3 Treg mRNA表達(dá)在阿維A干預(yù)前后沒有明顯變化(P0.05)。結(jié)論阿維A能夠通過降低Th17相關(guān)細(xì)胞因子的水平,減輕免疫炎癥反應(yīng),改善硬皮病小鼠皮膚和肺組織纖維化的程度。
[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 緯 -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 緯 -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.
【作者單位】： 首都醫(yī)科大學(xué)附屬北京世紀(jì)壇醫(yī)院皮膚科;中國醫(yī)學(xué)科學(xué)院中國協(xié)和醫(yī)科大學(xué)北京協(xié)和醫(yī)院風(fēng)濕免疫科;中國藏學(xué)研究中心北京藏醫(yī)院;
【基金】：北京市自然科學(xué)基金資助項目(7153168) 首都醫(yī)科大學(xué)附屬北京世紀(jì)壇醫(yī)院中青年學(xué)科骨干培養(yǎng)專項(2016-QB06)
【分類號】：R-332;R593.25
【正文快照】： 系統(tǒng)性硬化癥(systemic sclerosis,SSc)即硬皮病是以自身免疫性結(jié)締組織病變,累及皮膚和內(nèi)臟器官纖維化、微血管系統(tǒng)異常、免疫功能異常的病理三聯(lián)征為主要特點的疾病[1]。相應(yīng)的治療原則也是根據(jù)病理表現(xiàn)對癥治療,使用抗纖維化藥物、抗炎免疫抑制劑、血管活性藥物以及其他創(chuàng)

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