Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; The Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China.
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Brain Res Bull. 2019 Nov;153:30-38. doi: 10.1016/j.brainresbull.2019.08.006. Epub 2019 Aug 9.
Stressed oligodendrocytes (OLGs) activate microglia to produce an inflammatory response, and the impairment of mitochondria further aggravates OLG damage, which is the earliest pathological change in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. Matrine (MAT), a tetracyclic quinolizine alkaloid derived from the herb radix sophorae flavescentis, has been shown to effectively ameliorate clinical signs of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, the mechanisms underlying the effect of MAT treatment need to be further studied. In the present study, we show that MAT effectively suppressed ongoing EAE, and significantly reduced the expression of caspase-3 and alpha B-crystallin in OLGs, therefore lessen OLG apoptosis, microglial activation and inflammatory factors secretion. MAT treatment also reduced the content of cytochrome c and malondialdehyde, an oxidative stress marker, in the central nervous system. In contrast, the levels of autophagy-related proteins Beclin1, microtubule-associated protein l light chain 3 and glutathione peroxidase was upregulated, hence enhancing mitochondrial autophagy and alleviating the imbalance of the oxidation/antioxidation system caused by mitochondrial damage. Our research indicates that MAT is effective in treating EAE, at least in part, by protecting OLGs through inhibiting their apoptosis and enhancing mitochondrial autophagy.
应激性少突胶质细胞（OLGs）激活小胶质细胞产生炎症反应，而线粒体的损伤进一步加重了 OLG 的损伤，这是多发性硬化症（MS）的最早病理改变，MS 是一种中枢神经系统的炎症性脱髓鞘疾病。苦参碱（MAT）是从苦参根中提取的四环喹诺里嗪生物碱，已被证明能有效改善实验性自身免疫性脑脊髓炎（EAE）的临床症状，EAE 是 MS 的动物模型。然而，MAT 治疗效果的机制仍需要进一步研究。在本研究中，我们表明 MAT 能有效抑制进行性 EAE，并显著降低 OLG 中半胱天冬酶-3 和α B-晶状体蛋白的表达，从而减少 OLG 凋亡、小胶质细胞激活和炎症因子的分泌。MAT 治疗还降低了中枢神经系统细胞色素 c 和丙二醛（氧化应激标志物）的含量。相比之下，自噬相关蛋白 Beclin1、微管相关蛋白 l 轻链 3 和谷胱甘肽过氧化物酶的水平上调，从而增强了线粒体自噬，缓解了线粒体损伤引起的氧化/抗氧化系统失衡。我们的研究表明，MAT 通过抑制 OLG 凋亡和增强线粒体自噬来治疗 EAE 是有效的，至少部分如此。
