Rutin Attenuates Distraction Spinal Cord Injury by Inhibiting Microglial Inflammation Through Downregulation of P38 MAPK/NF-κB/STAT3 Pathway.

Distraction spinal cord injury (DSCI) is a severe complication following scoliosis correction surgery, for which there are currently no effective clinical treatments. This study aims to evaluate the inhibitory effects of rutin, a natural product, on inflammation in DSCI and to investigate the underlying mechanisms. In vitro, microglial cells were exposed directly to rutin to assess its ability to inhibit lipopolysaccharide (LPS)-induced inflammation. In rats with DSCI, the inhibitory effect of rutin on DSCI was evaluated using behavioral tests. mRNA sequencing was performed on spinal cord tissues to elucidate the mechanism of rutin's action. Rutin significantly suppressed the LPS-induced increase in inflammatory factors in microglial cells. In DSCI rats treated with rutin, scores in the Basso-Beattie-Bresnahan (BBB) were significantly improved. The mechanism of rutin's action was found to be related to its ability to reduce inflammatory infiltration in spinal cord tissue, protecting neurons from apoptosis and microstructural demyelination. Through assays of transcriptomic differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and RT-qPCR validation of the top DEGs, MAPK13 (also known as P38 MAPK) was finally identified as the key target gene in promoting DSCI development. Further molecular docking analysis indicated an interaction between rutin and P38 MAPK, supporting the rutin's action and the underlying mechanism in anti-inflammation. In conclusion, rutin effectively inhibited the development of DSCI in rats. The mechanism of rutin's action was associated with its activity in blocking the P38 MAPK/NF-κB/STAT3 pathway in the microglial cells of spinal cord. Rutin could be developed as a potential anti-DSCI drug for clinical applications.