Treg细胞抑制基质金属蛋白酶-9对类风湿性关节炎伴急性脑缺血损伤的研究进展

摘要/Abstract

摘要：

近些年的研究相继发现类风湿性关节炎（rheumatoid arthritis，RA）患者较健康人群更易得急性脑缺血等心脑血管疾病，RA的发生也会进一步加重急性脑缺血的发展。其中，基质金属蛋白酶-9（matrix metaloproteinase-9，MMP-9）可降解细胞外基质，破坏血脑屏障，引发炎性细胞和致炎因子等浸润，对构建脑缺血后炎性反应的级联放大网络起到重要作用。Treg细胞，即调节性T细胞（ regulatory T cells ），作为免疫抑制性细胞可多途径抑制MMP-9的活性，从而治疗急性脑缺血，缓解RA症状：（1）Treg细胞可通过负反馈阻断NF-κB通路，抑制MMP-9的活性；（2）Treg细胞可调控转化生长因子-β1（transforming growth factor-β1,TGF-β1)和肿瘤坏死因子(tumor necrosis factor-α,TNF-α)的表达抑制MMP-9的转录；（3）Treg细胞可通过转化急性脑缺血后被激活的小胶质细胞/巨噬细胞的极化类型，抑制小胶质细胞/巨噬细胞对MMP-9的促分泌作用，加强M2型小胶质细胞/巨噬细胞的免疫耐受；（4）Treg细胞可释放抑炎因子，拮抗致炎性的Th17细胞，平衡体内免疫，缓解RA和急性脑缺血所引发的炎症等。本文综述Treg细胞在RA合并急性脑缺血中通过抑制MMP-9的活性等起治疗作用，旨在为类风湿性关节炎合并急性脑缺血的有效治疗和研究提供参考。

关键词: 类风湿性关节炎, 急性脑缺血, 调节性T细胞, 基质金属蛋白酶-9

Abstract:

Recent studies have found that patients with rheumatoid arthritis (RA) are more likely to suffer from acute cerebral ischemia and other cardiovascular diseases than healthy people. RA further aggravated the development of acute cerebral ischemia. Matrix metalloproteinase-9 (MMP-9) may degrade the extracellular matrix, the damage of blood-brain barrier, the infiltration of inflammatory cells and pro-inflammatory cytokine. MMP-9 helps to build the series-wound amplifiers of inflammatory cascade reaction after cerebral ischemia. Treg cells can inhibit MMP-9 activity through multiple pathways to control acute cerebral ischemia and alleviate the symptoms of RA. First, Treg cells inhibit the activity of MMP-9 by blocking NF-κB pathway; Second, Treg cells can inhibit MMP-9 by regulating the expression of TGF-β1 and TNF-α; Third, Treg cells transform the polarization type of microglia/macrophage activated by acute cerebral ischemia to prevent MMP-9's secretion and the reinforce the immune tolerance of M2 microglia/macrophages; Fourth, Treg cells release anti-inflammatory cytokines to antagonize Th17 cells, to regulate immune balance and to alleviate inflammation induced by RA with acute cerebral ischemia. This article reviewed the therapeutic effects of Treg cells in treating RA with acute cerebral ischemia by inhibiting the activity of MMP-9 in hope of providing a reference for the effective treatment and research of RA with acute cerebral ischemia.

Key words: rheumatoid arthritis, acute cerebral ischemia, regulatory T cells, matrix metalloprotein-9

中图分类号:

R684.3| R743.31

沈忱，李运曼，夏念，徐丹，韩丹，陈仕杰. Treg细胞抑制基质金属蛋白酶-9对类风湿性关节炎伴急性脑缺血损伤的研究进展[J]. 中国临床药理学与治疗学, 2017, 22(7): 831-840.

SHEN Chen, LI Yunman, XIA Nian, XU Dan, HAN Dan, CHEN Shijie. Research on the inhibition of Treg cells on MMP-9 in rheumatoid arthritis with acute cerebral ischemia[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(7): 831-840.

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