Lidocaine relieves spinal cord ischemia-reperfusion injury via long non-coding RNA MIAT-mediated Notch1 downregulation

Microglial activation and inflammatory response play a critical role in spinal cord ischemia reperfusion injury (SCIRI). This study aimed to investigate whether lidocaine relieves SCIRI via modulating myocardial infarction-associated transcript (MIAT)-mediated Notch1 downregulation. Mouse SCIRI was induced by the obstruction of the aortic arch. Lidocaine was injected after reperfusion. Microglial activation and inflammatory response were assessed by Iba1, interleukin 1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α) levels. The interaction between MIAT and Notch1 was assessed by RNA pull-down and RNA immunoprecipitation assays. Lidocaine treatment relieved SCIRI by reducing Iba1 and serum TNF-α and IL-1β levels. After lidocaine treatment, MIAT expression was elevated in lipopolysaccharide-induced BV2 cells. The interference of MIAT and the overexpression of MIAT and Notch1 restored TNF-α and IL-1β levels in supernatants. Notch1 protein was existent in MIAT-pull-down compounds, and the expression of MIAT was markedly elevated in Notch1-immunoprecipitants. The overexpression of MIAT markedly promoted the degradation of Notch1 and increased the level of ubiquitin-bound Notch1 complex. The therapeutic effect of lidocaine on SCIRI mice could be reversed by adeno-associated virus-mediated MIAT knockdown. In conclusion, lidocaine treatment relieved SCIRI via inhibiting microglial activation and reducing the inflammatory response. The molecular mechanism was partly through MIAT-mediated Notch1 downregulation.