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2-(-2-苯并呋喃基)-2-咪唑啉通过调节大鼠缺血性脑卒中诱导的 Th17/Treg 平衡。

2-(-2-Benzofuranyl)-2-imidazoline reciprocally regulates Th17/Treg balance induced by ischemic stroke in rats.

机构信息

Department of Clinical Laboratory, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, China.

Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Pharmazie. 2020 Nov 1;75(11):586-589. doi: 10.1691/ph.2020.0634.

DOI:10.1691/ph.2020.0634
PMID:33239134
Abstract

Our group previously showed that 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) is a potent neuroprotective agent in the treatment of ischemic stroke in rats. As its mode of action was not well defined, we determined if its therapeutic effect includes altering an immune response to experimental ischemic stroke in rats. In the current study, 2-BFI significantly reduced stroke-induced brain infarct volume and it also decreased neurological deficits. Its anti-immune effects were determined based on flow cytometry measurements of both the 2-BFI-induced changes in the Th17/ Treg cell balance ratio and ELISA measurements of proinflammatory IL-17A and anti-inflammatory IL-10 cytokine expression levels in the brain and peripheral blood following ischemic strokes. 2-BFI blunted the stroke-induced increases in this ratio, which resulted from suppression of the rises in the Th17 cell number whereas the proportion of Treg cells increased. Stroke also induced increases in IL-17A expression levels whereas the IL-10 expression levels declined. 2-BFI treatment inhibited the rises in IL-17A expression levels whereas the corresponding declines in IL-10 were suppressed by this agent. Therefore, one of the neuroprotective effects of 2-BFI in the treatment of cerebral strokes stems from its suppression of rises in the Th17/Treg balance along with corresponding changes in related cytokines modulating development of this condition.

摘要

我们小组先前的研究表明,2-(-2-苯并呋喃基)-2-咪唑啉(2-BFI)是一种有效的治疗大鼠缺血性中风的神经保护剂。由于其作用机制尚未明确,我们确定其治疗效果是否包括改变大鼠实验性缺血性中风的免疫反应。在本研究中,2-BFI 显著降低了脑梗死体积,同时也降低了神经功能缺损。其免疫调节作用是基于流式细胞术检测 2-BFI 诱导的 Th17/Treg 细胞平衡比值的变化以及 ELISA 检测缺血性中风后大脑和外周血中促炎细胞因子 IL-17A 和抗炎细胞因子 IL-10 的表达水平来确定的。2-BFI 减弱了中风引起的该比值的升高,这是由于抑制了 Th17 细胞数量的增加,而 Treg 细胞的比例增加。中风还诱导了 IL-17A 表达水平的升高,而 IL-10 表达水平下降。2-BFI 治疗抑制了 IL-17A 表达水平的升高,而相应的 IL-10 下降被该药物抑制。因此,2-BFI 在治疗中风中的神经保护作用之一源于其抑制 Th17/Treg 平衡的升高以及相关细胞因子的变化,从而调节这种疾病的发展。

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