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富氢生理盐水通过逆转 Th1/Th2 失衡和上调 CD4+CD25+Foxp3+调节性 T 细胞、白细胞介素-10 和膜结合转化生长因子-β来改善豚鼠变应性鼻炎。

Hydrogen-Rich Saline Ameliorates Allergic Rhinitis by Reversing the Imbalance of Th1/Th2 and Up-Regulation of CD4+CD25+Foxp3+Regulatory T Cells, Interleukin-10, and Membrane-Bound Transforming Growth Factor-β in Guinea Pigs.

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, Tongji Hospital, Tongji University, Shanghai, 200065, China.

Department of Otolaryngology, Tongji Hospital, Tongji University, 389 Xincun road, Putuo District, Shanghai, 200065, China.

出版信息

Inflammation. 2018 Feb;41(1):81-92. doi: 10.1007/s10753-017-0666-6.

Abstract

It is well known that CD4+CD25+Foxp3+Treg cells play an important role in the development of allergic rhinitis (AR); the defect of cell numbers and functions contribute to AR. Hydrogen has been proven effective in alleviating symptoms of AR. We herein aim to verify the protective effects of hydrogen on CD4+CD25+Foxp3+Treg cells in guinea pigs with AR and to explore the effect of hydrogen-rich saline (HRS) on CD4+CD25+Foxp3+Treg cells in animals with AR and investigate the underlying anti-inflammatory mechanism. Eighteen guinea pigs were randomly divided into three groups (control group/AR group/AR-HRS group). The guinea pigs were injected with hydrogen-rich saline (AR-HRS group) for 10 days after sensitization. The control group was injected with an equal volume of normal saline. The number of sneezes, degree of runny nose, and nasal-rubbing movements were scored. Peripheral blood eosinophil count was recorded. The proportions of Th1/Th2 of the peripheral blood and the CD4+CD25+Foxp3+T cells in the CD4+T cells of the spleen and peripheral blood were determined by flow cytometry. The content of interleukin (IL)-10 and transforming growth factor (TGF)-β in the serum was detected by enzyme-linked immunosorbent assay (ELISA). The protein and mRNA expression of Foxp3, IL-10, and TGF-β were determined by Western blot, immunofluorescence, and real-time PCR analysis, respectively. Scores of symptoms, number of eosinophils,and nasal mucosa damage were dramatically reduced after HRS treatment. HRS increased the expression of Foxp3, IL-10, TGF-β, and number of CD4+CD25+Foxp3+Treg cells, which were reduced in AR. HRS also revised the dysregulation of Th1/Th2 balance. Both the number and biological activity of CD4+CD25+Foxp3+Treg cells increased with up-regulation of Th1/Th2 after HRS administration. HRS could play a protective role in attenuating AR through improving the proportion and functions of CD4+CD25+Foxp3+Treg cells.

摘要

众所周知,CD4+CD25+Foxp3+Treg 细胞在变应性鼻炎(AR)的发生发展中起重要作用;细胞数量和功能的缺陷导致 AR。氢气已被证明可有效缓解 AR 症状。本研究旨在验证氢气对 AR 豚鼠 CD4+CD25+Foxp3+Treg 细胞的保护作用,并探讨富氢生理盐水(HRS)对 AR 动物 CD4+CD25+Foxp3+Treg 细胞的影响,探讨其抗炎机制。18 只豚鼠随机分为三组(对照组/AR 组/AR-HRS 组)。致敏后,AR-HRS 组注射富氢生理盐水 10 天。对照组注射等体积的生理盐水。记录打喷嚏次数、流涕程度和鼻拭子动作评分。记录外周血嗜酸性粒细胞计数。采用流式细胞术检测外周血 Th1/Th2 比例及脾和外周血 CD4+T 细胞中 CD4+CD25+Foxp3+T 细胞的比例。酶联免疫吸附试验(ELISA)检测血清中白细胞介素(IL)-10 和转化生长因子(TGF)-β的含量。采用 Western blot、免疫荧光和实时 PCR 分析分别检测 Foxp3、IL-10 和 TGF-β 的蛋白和 mRNA 表达。HRS 治疗后症状评分、嗜酸性粒细胞数和鼻黏膜损伤明显减轻。HRS 增加了 Foxp3、IL-10、TGF-β 和 CD4+CD25+Foxp3+Treg 细胞的表达,而在 AR 中这些表达降低。HRS 还纠正了 Th1/Th2 平衡失调。HRS 给药后,通过上调 Th1/Th2,CD4+CD25+Foxp3+Treg 细胞的数量和生物学活性均增加。HRS 通过提高 CD4+CD25+Foxp3+Treg 细胞的比例和功能在减轻 AR 中发挥保护作用。

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