胶原诱导性关节炎小鼠脾脏T细胞合成儿茶酚胺增加

Increased synthesis of catecholamines by T cells in spleens from mice with collagen-induced arthritis

目的:探究胶原诱导性关节炎(collagen-induced arthritis,CIA)小鼠淋巴组织中T helper 1(Th1)细胞合成、储存、降解儿茶酚胺的变化,以进一步探讨Th1细胞来源的儿茶酚胺在类风湿关节炎(rheumatoid arthritis,RA)致病机制中所起的作用。方法:将DBA/1J小鼠随机分为正常对照组和CIA模型组。Ⅱ型胶原乳剂尾根部注射制备CIA小鼠模型。Western Blot法检测脾脏组织中Th1细胞转录因子T-bet、细胞因子干扰素-γ(interferon-γ,IFN-γ)和白细胞介素-2(interleukin-2,IL-2)的表达。免疫荧光双标法检测脾脏中T-bet分别与酪氨酸羟化酶(tyrosine hydroxylase,TH)、囊泡单胺转运体-2(vesicular monoamine transporter-2,VMAT-2)、单胺氧化酶(monoamine oxidase,MAO)的共定位。结果:与正常小鼠相比,CIA小鼠脾脏组织中T-bet、IFN-γ和IL-2的蛋白表达增加。小鼠脾脏中T-bet与TH、VMAT-2、MAO分别存在免疫荧光共定位。CIA组TH、VMAT-2及MAO单阳性细胞数以及分别的双阳性细胞数均显著增加(P<0.01)。结论:CIA小鼠Th1细胞合成、储存、降解儿茶酚胺的能力增强。Th1来源的儿茶酚胺参与了CIA的发生发展。

Objective： To investigate the changes in synthesis, storage and catabolism of catecholamines by T helper 1（Th1） cells in lymphoid tissues from collagen-induced arthritis（CIA） mice, for further understanding of the role Th1-derived catecholamines play in the pathogenic mechanism of rheumatoid arthritis（RA）. Methods： DBA/1J mice were randomly assigned to one of two groups （intact and CIA）. The CIA models were induced by type Ⅱ collagen（C Ⅱ ） injection from tails. Expressions of T-bet（transcription factor of Thl cells）, cytokines, interferon-γ/（IFN-γ） and interleukin-2（IL-2） in spleen tissues were detected by Western Blot. The colocalization of T-bet with hydroxylase （TH）, vesicular monoamine transporter-2 （VMAT-2）, and monoamine oxidase（MAO） in spleens, respectively, was determined by immunofluorescent staining. Results： Expressions of T-bet, IFN-γ and IL-2 in spleen tissues were increased in CIA mice compared with the intact mice. Colocalization of T-bet with TH, VMAT-2 and MAO was observed in both intact and CIA mice. TH~, VMAT-2＋ and MAO＋ cell numbers, as well as double positive-cell numbers were increased in CIA mice compared with the intact mice, respectively（P〈0.01）. Conclusions： Synthesis, storage and catabolism of Thl-derived catecholamines were increased in spleen from CIA mice. Thl-derived catecholamines play a role in development and progression of CIA.