【Animal Modeling】-The neuroprotective effect of artesunate on mice with experimental autoimmune encephalomyelitis and the effect of autophagy

  Objective: To investigate the neuroprotective effect of artesunate on experimental autoimmune encephalomyelitis (EAE) mice and the effect of autophagy.

  Methods: Forty-eight female C57BL/6 mice were randomly divided into a blank group, a model group, a low-dose artesunate group, and a high-dose group, a total of 4 groups, each with 12 mice. The MOG35-55 peptide was used to prepare the EAE model, Qing Artesunate (10mg/(kg·d), 50mg/(kg·d)) intraperitoneal injection of artesunate (10mg/(kg·d), 50mg/(kg·d)) was given to the low-dose artesunate group and the high-dose group for 10 consecutive days. Blue (LFB) staining was used to observe the demyelination, and Western blot was used to detect the expression of autophagy-related protein LC3-I and LC3-II.

  Results: None of the mice in the blank group had the disease. The mice in the model group and each dose of artesunate exhibited varying degrees of tail drooping, unstable walking, and hindlimb weakness. Compared with the model group, each dose group of artesunate , The incubation period of the onset, the delay of the peak period, the reduction of neurological function scores, the high-dose group and the lower-dose group had a significant effect (P<0.05), and="" the="" low-dose="" group="" high-dose="" had="" no="" statistical="" significance="" in="" peak="" period="" p="">0.05). ②LFB The staining shows that the myelin sheath of the model group is loosely arranged, disordered, and low-stained, and the myelin staining of each dose group of artesunate has improved. ③ Compared with the blank group, the Western blot detection of the model group shows LC3-I and LC3-II bands. The optical density value and LC3-II/LC3-I ratio increased (P<0.01); compared with the model group in each dose group of artesunate, LC3I, LC3II band optical density value and LC3-II/LC3-I ratio All decreased (P<0.01), and the high-dose group had a significant effect in the lower-dose group (P<0.05).

  Conclusion: Artesunate has a neuroprotective effect on EAE mice, reducing the demyelination of brain tissue, and the mechanism of action may be related to the reduction of autophagy by down-regulating LC3-I, LC3-II and LC3-II/LC3-I 。