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Research Article

氨基氧乙酸通过调节效应性和调节性淋巴细胞亚群之间的平衡抑制实验性自身免疫性葡萄膜炎

卷 20, 期 8, 2020

页: [624 - 632] 页: 9

弟呕挨: 10.2174/1566524020666200211112219

价格: $65

摘要

目的：一种小分子化合物，氨基氧乙酸(AOA)，已被证明可调节实验性自身免疫性脑脊髓炎(EAE)。本研究旨在探讨AOA是否对实验性自身免疫性葡萄膜炎(EAU)的发生有类似作用，并进一步探讨该药物的潜在机制。 方法：用光感受器视黄醛结合蛋白肽651-670 (IRBP 651-670)免疫C57BL/6J小鼠诱导EAU。经水诱导后第10 ~ 14天腹腔注射AOA(500μg或750μg)或对照组。通过临床和组织学评分评估严重程度。用伊文思蓝检测血液视网膜屏障的完整性。流式细胞术检测脾Th1、Th17和Foxp3+ Treg细胞频率。ELISA法检测细胞因子的产生。RT-PCR检测IL-17、IFN-γ、IL-10 mRNA的表达。Western Blotting检测p-Stat1和NF-κB的表达。 结果：临床和组织病理学检查发现，AOA能显著抑制EAU的严重程度。AOA可以缓解血液视网膜屏障(BRB)的渗漏。功能研究发现，与对照组相比，EAU小鼠的Th1和Th17细胞频率下降，Treg细胞频率增加。进一步的研究表明，AOA不仅下调了IFN-γ、IL-17等促炎细胞因子的产生，而且上调了IL-10等抗炎细胞因子的表达，这可能是通过抑制p-Stat1和NF-κB的表达引起的。 结论：本研究表明，AOA通过调节调节性和致病性淋巴细胞亚群之间的平衡，抑制EAU的严重程度和发展。

关键词: 实验自身免疫性葡萄膜炎，氨基氧乙酸(AOA)， Th17细胞，Th1细胞，Treg细胞，葡萄膜炎。

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