红景天苷通过靶向信号转导和转录激活因子3（STAT-3）调节Th17/Treg失衡并促进脑缺血再灌注损伤中的缺血耐受。
Salidroside regulates imbalance of Th17/Treg and promotes ischemic tolerance by targeting STAT-3 in cerebral ischemia-reperfusion injury.
作者信息
Yin Lele, Ouyang Dongyun, Lin Lihong, Xin Xiufeng, Ji Yuhua
机构信息
Department of Clinical laboratory, the First Affiliated Hospital of Jinan University, Guangzhou, China.
Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, China.
出版信息
Arch Med Sci. 2019 May 24;17(2):523-534. doi: 10.5114/aoms.2019.85349. eCollection 2021.
INTRODUCTION
The balance between Th17 and Treg cells controls the immune response and is an important regulator of helper T cells acting on autoimmune diseases. Focal cerebral ischemia-reperfusion injury can induce imbalance of Th17/Treg cells in the brain and the peripheral immune system of rats. The aim of this study was to investigate the effect of salidroside (Sal) on the ratio of Th17 and Treg cells in an adult rat model of middle cerebral artery occlusion (MCAO).
MATERIAL AND METHODS
Forty rats were divided into 4 groups: normal group, sham group, surgery group, and Sal group. After treatment, the neurological deficits in rats were evaluated. Peripheral blood mononuclear cells were isolated and the count of Th17 and Treg cells was detected by flow cytometry. The infarct size and expression of RORγt and Foxp3 were detected in rat brain tissue. Rat spleen cells were isolated, CD4 T cells were purified by immunomagnetic beads. Treg cells were induced by adding cytokine TGF-β. Th17 cells were induced by adding cytokine IL-6. The expression of STAT-3 was inhibited by SiRNA, and the effect of Sal on the differentiation of Th17/Treg cells was analyzed. The expression levels of IL-6, TNF-α, MCP-1, STAT-3 and NF-κ-B2 proteins were examined.
RESULTS
The results show that MCAO can induce an imbalance of Th17 and Treg cells in peripheral blood of rats. Sal treatment can significantly reduce the neurological deficit and infarct size of MCAO rats, reverse the oxidative stress of rat brain tissue, and inhibit the apoptosis of brain cells in MCAO rats. In the brain tissue of MCAO rats, Sal could significantly inhibit the expression of IL-6, TNF-α, MCP-1, STAT-3 and NF-κ-B2. Down-regulation of STAT-3 significantly reversed the therapeutic effects of Sal treatment.
CONCLUSIONS
Our results indicate that Sal can increase the tolerance of rat brain tissue to ischemia, inhibit cell apoptosis and reduce oxidative stress by targeting STAT-3.
引言
Th17细胞与调节性T细胞（Treg细胞）之间的平衡控制着免疫反应，是作用于自身免疫性疾病的辅助性T细胞的重要调节因子。局灶性脑缺血再灌注损伤可诱导大鼠脑内及外周免疫系统中Th17/Treg细胞失衡。本研究旨在探讨红景天苷（Sal）对成年大鼠大脑中动脉闭塞（MCAO）模型中Th17和Treg细胞比例的影响。
材料与方法
40只大鼠分为4组：正常组、假手术组、手术组和Sal组。治疗后，评估大鼠的神经功能缺损。分离外周血单个核细胞，采用流式细胞术检测Th17和Treg细胞计数。检测大鼠脑组织梗死面积及维甲酸相关孤儿受体γt（RORγt）和叉头框蛋白3（Foxp3）的表达。分离大鼠脾细胞，通过免疫磁珠纯化CD4 + T细胞。添加细胞因子转化生长因子-β（TGF-β）诱导Treg细胞。添加细胞因子白细胞介素-6（IL-6）诱导Th17细胞。用小干扰RNA（SiRNA）抑制信号转导子和转录激活子3（STAT-3）的表达，分析Sal对Th17/Treg细胞分化的影响。检测白细胞介素-6、肿瘤坏死因子-α、单核细胞趋化蛋白-1、信号转导子和转录激活子3及核因子κB2（NF-κB2）蛋白的表达水平。
结果
结果显示，MCAO可诱导大鼠外周血中Th17和Treg细胞失衡。Sal治疗可显著降低MCAO大鼠的神经功能缺损和梗死面积，逆转大鼠脑组织的氧化应激，并抑制MCAO大鼠脑细胞凋亡。在MCAO大鼠脑组织中，Sal可显著抑制白细胞介素-6、肿瘤坏死因子-α、单核细胞趋化蛋白-1、信号转导子和转录激活子3及核因子κB2的表达。STAT-3的下调显著逆转了Sal治疗的效果。
结论
我们的结果表明，Sal可通过靶向STAT-3增加大鼠脑组织对缺血的耐受性，抑制细胞凋亡并减轻氧化应激。
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