Study on the mechanism of salidroside regulating lncRNA HOTAIR/NF-κB to promote motor function after spinal cord injury

Objective: To investigate the effect of salidroside (SAL) regulating long non-coding RNA HOX transcript antisense RNA (lncRNA HOTAIR) on motor function after spinal cord injury (SCI). Methods: Twenty-seven SD rats were randomly divided into sham surgery group, SCI group, and SCI+SAL group. A rat model of SCI was established using the modified Allen’s method. BBB scoring was used to assess the motor function of the rats’hind limbs. Hematoxylin-eosin (HE) staining and Nissl staining were used to observe the spinal cord tissue structure and the number of neurons. The expression of HOTAIR and related inflammatory factors was determined by reverse transcription- quantitative PCR (RT-qPCR). The lncRNA HOTAIR overexpressed astrocytes were cultured in vitro, and then divided into 8 groups along with primary astrocytes: control group and SAL group with different concentrations (6.25 μg/mL, 12.5 μg/mL, 25 μg/mL, 50 μg/mL, 100 μg/mL, 200 μg/mL and 400 μg/mL). The cell survival rate was assessed using the cell counting kit-8 (CCK-8) method. The model of secondary SCI inflammation was established using Lipopolysaccharide (LPS), and SAL was administered at varying concentrations. The gene expression of lncRNA HOTAIR, IL-6, TNF-α was detected by RT-qPCR, and the protein expression of NF-κB pathway and inflammatory factors was determined by western blotting and enzymelinked immunosorbent assay (ELISA), respectively. Results: The intervention of SAL significantly enhanced the BBB score in SCI rats, mitigated tissue structure destruction and neuronal damage, and down-regulated the expression of HOTAIR and inflammatory factors (TNF-α, IL-6) following SCI. In vitro studies revealed no significant alteration in astrocyte survival rates across different doses groups of SAL compared with the control group. Further investigations demonstrated that SAL could modulate lncRNA HOTAIR to reduce the expression of inflammatory factors in LPS-stimulated astrocytes, while also targeting lncRNA HOTAIR to down-regulate the expression of p-NF-κB p65, p-IκB-α, IKKβ proteins and inflammatory factors. Conclusion: SAL can promote the recovery of motor function in SCI rats, and its mechanism may be related to reducing inflammation and inhibiting the expression of lncRNA HOTAIR.