Propofol Protects against Cerebral Ischemia/Reperfusion Injury by Down-Regulating Long Noncoding RNA SNHG14

Cerebral ischemia-reperfusion (CI/R) injury is a serious central nervous system disease. Propofol (PPF) exerts a neuroprotective effect in CI/R injury; the underlying cause is still unclear. Here, we cultured mouse hippocampal neuron (HT22 cells) in oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to mimic CI/R injury in vitro. PPF treatment promoted cell viability and reduced apoptotic cells in the OGD/R-treated HT22 cells, which was effectively abrogated by SNHG14 overexpression. Moreover, we constructed a CI/R injury mouse model on C57BL/6J mice by middle cerebral artery occlusion/reperfusion (MCAO/R), followed by administration of PPF. PPF reduced neuronal damage and loss, enhanced glial cell hyperplasia, and ameliorated cerebral cortex tissue damage and brain infarct in MCAO/R-induced mice. SNHG14 overexpression aggravated MCAO/R-induced CI/R injury in mice. Furthermore, SNHG14 promoted the expression of Atg5 and Beclin 1 via competitively binding miR-30b-5p, which contributed to activate autophagy and apoptosis in HT22 cells. In addition, the levels of p-p38 and p-SP1 were reduced in the OGD/R-treated HT22 cells in the presence of PPF. SP1 interacted with the promoter of SNHG14 and elevated the expression of SNHG14. PPF treatment inhibited the SP1-mediated up-regulation of SNHG14. In conclusion, this work demonstrates that PPF inhibits SNHG14 expression though the p38 MAPK signaling pathway. SNHG14 promotes Atg5 and Beclin 1 expression by sponging miR-30b-5p and thus activates autophagy and aggravates CI/R injury.