α1-肾上腺素受体对胶原诱导性关节炎小鼠Treg细胞功能的影响*

doi:10.12047/j.cjap.6127.2021.071

摘要/Abstract

摘要： 目的: 利用胶原诱导性关节炎 (CIA) 模型小鼠,探讨去甲肾上腺素 (NE) 及其α1-肾上腺素受体 (AR ) 对CIA小鼠Treg细胞的作用。方法: 雄性DBA/1小鼠 32 只,随机分为对照组 (n=8) 和CIA模型组 (n=24)。II型胶原 (CII) 乳剂100 μl 尾根部注射DBA/1小鼠制备CIA小鼠模型,在初次免疫后第 41 日,用免疫荧光法检测小鼠脾脏中CD4⁺T与α1-AR的共定位情况;用Western blot法检测小鼠踝关节和脾脏中α1-AR的蛋白表达。分离纯化CIA小鼠脾脏中CD4⁺ T细胞,用抗CD3和抗CD28的单克隆抗体刺激CD4⁺T细胞,进行细胞培养,分为未加药组和加药组,加药组用NE或α1-AR激动剂苯肾上腺素 (phenylephrine) 处理细胞,用流式细胞术检测CIA小鼠CD4⁺T细胞中Treg的细胞数;用Western blot法检测CIA小鼠CD4⁺T中转化生长因子-β (TGF-β) 和IL-10的蛋白表达。结果: CD4⁺ T细胞能够表达α1-AR;与对照组相比,CIA小鼠踝关节和脾脏中α1-AR的蛋白表达显著降低(P＜0.01);与未加药的CIA小鼠的CD4⁺ T细胞相比,NE加入后的CIA小鼠CD4⁺ T细胞中Treg细胞的功能显著增强(P＜0.01);α1-AR激动剂phenylephrine加入后的CIA小鼠CD4⁺ T细胞中Treg细胞的功能显著增强(P＜ 0.01)。结论: 激活CIA小鼠CD4⁺ T细胞上的α1-AR可增强Treg细胞的功能,促进CD4⁺ T细胞向Treg细胞方向分化,发挥抗炎作用。

关键词: 小鼠, 胶原诱导性关节炎, Treg细胞, 去甲肾上腺素, α1-肾上腺素受体

Abstract: Objective: An animal model of collagen-induced arthritis (CIA) was used to investigate the effects of norepinephrine (NE) and α1-adrenoreceptor (α1-AR) on Treg cells in CIA. Methods: Thirty-two male DBA/1 mice were randomly divided into control group and CIA model group. CIA was prepared by intradermal injection of collagen type II (CII, 100 μl) at the tail base of DBA/1 mice. On the 41^th day following primary immunization, co-expression of CD4⁺T and α1-AR in mouse spleens was observed. Protein expressions of α1-AR in the ankle joints and the spleens of mice were measured by Western blot analysis. The CD4⁺ T cells were isolated from the mouse spleen tissues in CIA mice and treated with NE or α1-AR agonist phenylephrine. Percentage of Treg cells in mouse CD4⁺ T cells of CIA mice was determined by flow cytometry. Expressions of α1-AR, transforming growth factor-β (TGF-β) and IL-10 in CD4⁺T cells of CIA mice were assessed by Western blot. Results: Co-expression of CD4 and α1-AR was observed in spleens of both intact and CIA mice. Compared with intace mice, α1-AR expressions in the ankle joints and spleens were down-regulated in CIA mice. NE increased the function of Treg cells in CD4⁺ T cells of CIA mice compared with that of nothing-treated CD4⁺T cells of CIA mice. Moreover, the α1-AR agonist phenylephrine increased the Treg cell function in CD4⁺ T cells of CIA mice relative to that of nothing-treated CD4⁺T cells of CIA mice. Conclusion: Activating α1-AR on CD4⁺T cells of CIA mice enhances Treg cell function,facilitating a shift of CD4⁺T cells toward Treg polarization.

Key words: mice, collagen-induced arthritis, Treg cells, norepinephrine, α1-adrenoreceptor

中图分类号:

R392

王小琴, 石卉, 方小霞, 彭聿平. α1-肾上腺素受体对胶原诱导性关节炎小鼠Treg细胞功能的影响^*[J]. 中国应用生理学杂志, 2021, 37(5): 449-453.

WANG Xiao-qin, SHI Hui, FANG Xiao-xia, PENG Yu-ping. Effects of α1-adrenoreceptor on Treg cell function in collagen-induced arthritis[J]. CJAP, 2021, 37(5): 449-453.

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α1-肾上腺素受体对胶原诱导性关节炎小鼠Treg细胞功能的影响^*

Effects of α1-adrenoreceptor on Treg cell function in collagen-induced arthritis

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