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经典 Wnt/β-连环蛋白信号通路在实验性自身免疫性神经炎病理过程中的动态表达。

The dynamic expression of canonical Wnt/β-catenin signalling pathway in the pathologic process of experimental autoimmune neuritis.

机构信息

Department of Neurology, Wuhan University, Renmin Hospital, Wuhan, Hubei Province, P.R. China.

出版信息

Int J Neurosci. 2020 Nov;130(11):1109-1117. doi: 10.1080/00207454.2020.1725511. Epub 2020 Feb 10.

DOI:10.1080/00207454.2020.1725511
PMID:32009498
Abstract

Guillain-Barré syndrome (GBS), an autoimmune disease and an acute inflammation disorder, is currently the most frequent cause of acute flaccid paralysis worldwide. EAN, an animal model of GBS, is a CD4+ T cell-mediated autoimmune disease of the PNS. Wnt/β-catenin signals are critically important to several fundamental aspects of peripheral nerve development and play a crucial role in Schwann cell proliferation. Here, we investigate the role of Wnt/β-catenin signalling cascades in EAN rats. 28 male Lewis rats weighing 170 ± 10 g were randomly divided into control group ( = 7) and EAN groups (Early group; Peak group and Recovery group.  = 7 per group). EAN rats were immunized with P2 peptide; weighed daily, and the neurologic signs of EAN were evaluated every day. The sciatic nerve was taken on the days 10, 17, and 30 p.i. for H&E staining, transmission electron microscopy and immunohistochemical staining; blood samples were collected weekly from caudal vein to detect IFN-γ, IL-4, TGF-β1; and the sciatic nerve was taken to examinate the dynamics expression of Wnt/β-catenin pathway molecules. In our study, we chose tail-root injection to better model GBS. Moreover, we observed that IFN-γ levels paralleled clinical EAN, and the levels of TGF-β1 and IL-4 gradually increased and peaked in the recovery phase. In addition, we have shown that canonical Wnt signalling is upregulated and reached a peak in the late recovery phase. Our findings suggest that Wnt/β-catenin signalling is associated with the promotion of remyelination in EAN rats.

摘要

格林-巴利综合征(GBS)是一种自身免疫性疾病和急性炎症性疾病,是目前全球最常见的急性弛缓性瘫痪的原因。EAN,GBS 的动物模型,是一种 CD4+T 细胞介导的周围神经系统自身免疫性疾病。Wnt/β-连环蛋白信号对于周围神经发育的几个基本方面至关重要,并在 Schwann 细胞增殖中发挥关键作用。在这里,我们研究了 Wnt/β-连环蛋白信号通路在 EAN 大鼠中的作用。28 只体重为 170 ± 10 g 的雄性 Lewis 大鼠被随机分为对照组(n = 7)和 EAN 组(早期组;高峰组和恢复期组,每组 n = 7)。EAN 大鼠用 P2 肽免疫;每天称重,并每天评估 EAN 的神经症状。在感染后第 10、17 和 30 天取坐骨神经进行 H&E 染色、透射电镜和免疫组织化学染色;每周从尾静脉采集血液样本以检测 IFN-γ、IL-4、TGF-β1;取坐骨神经检测 Wnt/β-连环蛋白通路分子的动态表达。在我们的研究中,我们选择尾根注射来更好地模拟 GBS。此外,我们观察到 IFN-γ 水平与临床 EAN 平行,而 TGF-β1 和 IL-4 的水平在恢复期逐渐升高并达到峰值。此外,我们已经表明,经典 Wnt 信号通路被上调,并在后期恢复阶段达到峰值。我们的研究结果表明,Wnt/β-连环蛋白信号通路与 EAN 大鼠的髓鞘再生促进有关。

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