Abstract：
Oligodendrocyte (OL) death and remyelination failure lead to progressive neurological deficits in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Matrine (MAT), a quinolizidine alkaloid component derived from the root of Sophora flavescens, has the capacity to effectively inhibit central nervous system (CNS) inflammation and to promote neuroregeneration. In the present study we explored its regulatory mechanism on the Wnt/β-catenin/TCF7L2 pathway, a negative modulator for myelination, in MOG35--55 peptide-induced EAE. Our results clearly indicate that MAT treatment reduced the activation of Wnt3a and β-catenin in the CNS of EAE mice, accompanied by the activation of GSK3β and decreased expression of cyclin D1 and Axin2, two target genes of the Wnt3a/β-catenin pathway. In addition, MAT increased OL maturation and myelination, as evidenced by the decreased number of NG2+Olig2+ cells and the increased numbers of MBP+ and CC1+Olig2+ cells. Taken together, these findings indicate that MAT treatment promoted the maturation of OLs and myelin repair, which is closely related to the modulation of the Wnt/β-catenin/TCF7L2 signaling pathway.
摘要：
少突胶质细胞（OL）死亡和髓鞘再生失败导致多发性硬化（MS）及其动物模型的进行性神经功能缺损，实验性自身免疫性脑脊髓炎（EAE）。苦参碱(MAT),一种来自苦参根的喹诺酮苷生物碱成分，具有有效抑制中枢神经系统（CNS）炎症和促进神经再生的能力。在本研究中，我们探讨了其对Wnt/β-catenin/TCF7L2通路的调控机制，髓鞘形成的负调节剂，在MOG35--55肽诱导的EAE中。我们的结果清楚地表明，MAT治疗降低了EAE小鼠CNS中Wnt3a和β-catenin的激活，伴随着Wnt3a/β-catenin途径的两个靶基因GSK3β的激活和cyclinD1和Axin2的表达降低。此外,MAT增加了OL成熟和髓鞘形成，如NG2+Olig2+细胞的数量减少和MBP+和CC1+Olig2+细胞的数量增加所证明的。一起来看,这些发现表明MAT治疗促进了OLs的成熟和髓鞘修复，与Wnt/β-catenin/TCF7L2信号通路的调控密切相关。
