Effect of remifentanil on the intervertebral disc of rats with intervertebral disc degeneration and its mechanism

Abstract:

Objective To observe the protective effect of remifentanil on intervertebral disc of rats with intervertebral disc degeneration （IDD），and to explore its mechanism of action.Methods A total of 40 healthy SD rats were randomly divided into sham-operation group，model group，low-dose，middle-dose and high-dose remifentanil groups，8 cases in each group. IDD models were constructed by fibrous annulus puncturing. After modeling，low-dose，medium-dose and high-dose remifentanil groups were given intravenous injection of remifentanil through tail vein at rates of 0.2，0.6 and 1.2 μg/（kg·min） for 30 minutes，while model group and sham operation group were given the same volume of normal saline. The pathological changes of intervertebral disc tissues were observed by hematoxylin-eosin（HE） staining. The levels of serum tumor necrosis factor α（TNF-α），interleukin 6（IL-10） and interleukin 1β（IL-1β） were detected by enzyme linked immunosorbent assay（ELISA）. The expressions of peroxisome proliferator-activated receptor-1α（PGC-1α），mitochondrial transcription factor A（TFAM），cysteine aspartic protease-1（Caspase-1），gasdermin D（GSDMD），NOD-like receptor family pyrin domain containing 3（NLRP3），hypoxia-inducible factor 1α（HIF-1α） and vascular endothelial growth factor（VEGF） in intervertebral disc tissues were detected by Western blot.Results Compared with sham operation group，nucleus pulposus was shrunk，arrangement of fibrous annulus was disordered and the number of nucleus pulposus cells was decreased in model group. The levels of serum TNF-α，IL-6 and IL-1β were increased（P<0.05）. The expression levels of PGC-1α and TFAM in intervertebral disc tissues were decreased，and expression levels of Caspase-1，GSDMD，NLRP3，HIF-1α and VEGF were increased（P<0.05）. Compared with model group，disorders of fibrous annulus were significantly improved in medium-dose and high-dose remifentanil groups，and number of nucleus pulposus cells was significantly increased. The levels of serum TNF-α，IL-6 and IL-1β were decreased（P<0.05）. The expression levels of PGC-1α and TFAM in intervertebral disc tissues were increased，and expression levels of Caspase-1，GSDMD，NLRP3，HIF-1α and VEGF were decreased（P<0.05）.Conclusion Remifentanil can improve IDD in rats，and its mechanism is related to inhibiting inflammatory response and pyroptosis of intervertebral disc，and regulating HIF-1α/VEGF signaling pathways.