Treadmill training improves respiratory function in rats after spinal cord injury by inhibiting the HMGB1/TLR-4/NF-κB signaling pathway

•Treadmill training improves motor and respiratory functions of SCI rats.•Treadmill training inhibits inflammatory response in lung tissue of rats after SCI.•Screening of differentially expresses mRNAs and KEGG enrichment analysis in NF-kappa B signal pathway.•Validation of transcriptome data using qRT-PCR, Western Blot, immunohistochemistry, and immunofluorescence.•Treadmill exercise training inhibits the inflammatory response in the lung tissue of rats after SCI by regulating the HMGB1/TLR-4/NF-κB signaling pathway. To investigate the effects of treadmill training on lung injury and HMGB1/TLR4/NF-κB after spinal cord injury (SCI) in rats. A total of 108 female SD rats were randomly divided into three groups: sham operation group, SCI brake group, and SCI exercise group. The rats in the SCI exercise group began treadmill training on the 3rd day after the operation. The rats in the SCI brake group underwent braking treatment. The lung tissues were obtained on the 3rd, 7th, and 14th days after exercise. Locomotor functional recovery was determined using the BBB scores and inclined plane test. Respiratory function was determined via abdominal aortic blood gas analysis. HE staining was used to detect pathological changes in rat lung tissue. RNA sequencing was used to identify differentially expressed genes at different phases in each group of lung tissues. HMGB1, TLR4, and NF-κB in lung tissue were detected using immunohistochemistry and immunofluorescence. Detection of HMGB1 levels in serum, spinal cord tissues and lung tissues by ELISA. HMGB1, TLR4, NF-κB, IL-1β, IL-6, TNF-α mRNA, and protein expression levels were detected via qRT PCR and western blot. Motor and respiratory functions significantly decreased after SCI (P