不饱和脂肪酸衍生物DCLAA对实验性自身免疫性脑脊髓炎的治疗作用

Abstract

Multiple sclerosis is a chronic inflammatory disease characterized by demyelination in the central nervous system (CNS). The existing drugs for multiple sclerosis treatment carry significant side effects. The aim of this study was to investigate the safety and effect of a new compound N, N′-dicyclohexyl-N-linoleic acylurea (DCLAA) on experimental autoimmune encephalomyelitis (EAE), the principal multiple sclerosis animal model. Results showed that DCLAA had low toxicity, and DCLAA significantly inhibited the EAE progression and reduced the dosage requirements of methylprednisolone. After DCLAA treatment, the activation of microglia and astrocytes in the CNS was reduced. The expression of proinflammatory cytokines decreased, whereas the expression of anti-inflammatory cytokines increased. DCLAA reduced the number of peripheral T cells and CNS infiltration in EAE mice. Moreover, DCLAA attenuated the proliferation and induced the apoptosis of myelin oligodendrocyte glycoprotein (MOG)-specific T cells. These results indicate that DCLAA exhibit low toxicity and is able to alleviate the clinical symptoms of EAE by reducing neuroinflammation and suppressing the survival of peripheral T cells.