LncRNA SNHG3 Promotes Sevoflurane-Induced Neuronal Injury by Activating NLRP3 via NEK7

Early exposure to sevoflurane may cause brain tissue degeneration; however, the mechanism involved in this process has not been explored. In this study, we investigated the role of long non-coding RNA small nucleolar RNA host gene 3 (lncRNA SNHG3) in sevoflurane-induced neuronal injury.

The injury models of HT22 and primary cultures of neurons were constructed using sevoflurane treatment. The WST-8 reduction was detected by CCK-8 assay, the level of inflammatory factors was detected by enzyme-linked immunosorbent assay (ELISA), and cell pyroptosis was detected by flow cytometry. The expression of genes and proteins was detected by qRT-PCR and Western blot, respectively. The level of β-tubulin III in primary cultures of hippocampal neurons was analyzed by immunofluorescence. The relationship among SNHG3, PTBP1 and NEK7 was confirmed by RIP assay.

The expression of SNHG3 and NEK7 were enhanced in sevoflurane-treated HT22 cells. Sevoflurane inhibited the WST-8 reduction in a concentration-dependent manner, promoted the pyroptosis, and increased pyroptosis-related protein expression. SNHG3 knockdown significantly inhibited sevoflurane-induced pyroptosis and inflammatory injury in HT22 cells and primary cultures of neurons. Furthermore, SNHG3 regulated NEK7 expression by binding to PTBP1. NEK7 knockdown reversed the decrease in WST-8 reduction, inhibited pyroptosis, and decreased the release of inflammatory factors and pyroptosis-related protein expression by inactivation of NLRP3 signaling in sevoflurane-induced HT22 cells. Moreover, NEK7 overexpression attenuated the effect of SNHG3 knockdown on neuronal pyroptosis and inflammation injury.

Downregulation of SNHG3 attenuates sevoflurane-induced neuronal inflammation and pyroptosis by mediating the NEK7/NLRP3 axis, suggesting that SNHG3 could be a potential target gene for neuronal injury.