Low-dose lipopolysaccharide inhibits spinal cord injury-induced neuronal apoptosis by regulating autophagy through the lncRNA MALAT1/Nrf2 axis

Spinal cord injury (SCI) is a neurological disease associated with a high disability rate. Low-dose lipopolysaccharide (LPS) has been reported to activate cross-immune tolerance and alleviate the effects of various traumatic stimuli. The present study aimed to explore the effect of LPS on SCI and the potential molecular mechanism.

Low-dose LPS exhibited a protective role on SCI by activating autophagy and suppressing nerve cell apoptosis via the lncRNA MALAT1/Nrf2 axis.

Male Sprague-Dawley (SD) rats were used to established an in vivo SCI model and were intraperitoneally injected with lentivirus particles encoding a MALAT1 small interfering RNA (siRNA) on day 10 prior to SCI and with 0.2 mg/kg LPS 72 h prior to SCI. Basso, Beattie, and Bresnahan (BBB) scoring; HE staining; and TUNEL assay were used to assess neurological function and pathophysiological changes. Western blot and immunohistochemistry (IHC) were used to detect cell autophagy and Nrf2 nuclear translocation. PC12 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to establish an in vitro SCI model. In vitro SCI model cells were pretreated with LPS and transfected with siMALAT1 or MALAT1 overexpression plasmid aimed at knocking down MALAT1 or overexpressing MALAT1. The cell counting kit-8 (CCK-8) assay was used to measure the toxicity of LPS towards PC12 cells. Flow cytometry and immunofluorescence analysis were performed to investigate cell apoptosis and Nrf2 nuclear translocation.

SCI rats preconditioned with low-dose LPS had higher BBB scores, reduced SCI injury, increased MALAT1 expression and activated autophagy and Nrf2 nuclear translocation in the in vivo SCI model. In the in vitro SCI model, low-dose LPS treatment suppressed the apoptotic ratio of PC12 cells, increased MALAT1 expression, activated autophagy, and promoted Nrf2 nuclear translocation. Silencing MALAT1 exacerbated OGD/R injury in vitro and weakened the protective effect of low-dose LPS. Overexpression of MALAT1 inhibits OGD/R-induced apoptosis by inducing autophagy and promoting Nrf2 nuclear translocation. This was also been confirmed in animal experiments, silencing MALAT1 blocked the promotion of Nrf2 by low-dose LPS and the alleviated of SCI apoptosis. Conclusions: Low-dose LPS exhibited a protective role on SCI by activating autophagy and suppressing nerve cell apoptosis via the lncRNA MALAT1/Nrf2 axis.