Journal of Tissue Engineering and Reconstructive Surgery ›› 2024, Vol. 20 ›› Issue (4): 422-.

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Neuroprotective effect of Liraglutide(LRG)on spinal cord injury(SCI)in rats by inhibiting ferroptosis

  

  • Online:2024-08-01 Published:2024-09-11

Abstract:

Objective To observe the neuroprotective effect of liraglutide( LRG) on spinal cord injury( SCI) rats, and to explore whether its mechanism is related to inhibiting ferroptosis. Methods A total of 90 female Wistar rats were randomly divided into sham group( n=30), SCI group( n=30) and LRG+SCI group( n=30). A rat model of SCI was established using the modified Allen’s method. For the SCI+LRG group, LRG (200 µg/kg) was administered immediately via subcutaneous injection( s.c.) following SCI, and then subsequently given once a day for the next ten days. Animals in both the sham and SCI group were administrated with equal volumes of sterile PBS. The iron content and glutathione( GSH) level in spinal cord were detected by the kit at 24, 48 and 72 h after operation. The expression levels of xCT and GPX4 protein were analyzed by Western blot. The BBB locomotion rating scale was used to investigate the hindlimb function 1, 3, 7, 14, 28 days after injury. HE staining and Nissl Staining were performed to evaluate the structural damage and surviving neurons around the injured area 28 days after operation, and the neuron apoptosis was detected by immunofluorescence staining. Results. Compared with the sham operation group, the iron content in SCI group was significantly increased within 3 days after injury (P<0.05), and GSH level was significantly decreased (P<0.05). LRG treatment effectively decreased the iron contents in injured spinal cords( P<0.05), and increased GSH level (P<0.05). In addition, LRG treatment significantly increased the expression levels of xCT and GPX4 in injured spinal cords( P<0.01). Compared with SCI group, the BBB score of LRG group was significantly higher at 7, 14 and 28 days after injury (P<0.05). HE staining and Nissl staining showed that cavity of damaged regions of LRG group was lower than that of SCI group (P<0.05), and the number of motoneurons in the spinal ventral horn of rat treated with LRG was higher than that of SCI group (P<0.05). Immunofluorescence staining showed that the ratio of cleaved-caspase 3-positive neurons was remarkably increased after SCI( P<0.05) and LRG significantly reduced the ratio of cleaved-caspase 3-positive neurons( P<0.05). Conclusion LRG treatment after SCI may promote SCI repair, protect damaged neurons and restore motor function through inhibiting ferroptosis in the microenvironment at the lesion site.

Key words: Liraglutide,  Ferroptosis,  Spinal cord injury,  Neuroprotection,  Motor function