MiR-34a targets SIRT1 to reduce p53 deacetylation and promote sevoflurane inhalation anesthesia-induced neuronal autophagy and apoptosis in neonatal mice

Abstract

This study is to investigate the function of miR-34a and interactions between miR-34a, SIRT1, and p53 in sevoflurane-induced neuronal apoptosis and autophagy in neonatal mice. A mouse model was established by inhalation anesthesia with sevoflurane and injected with genetic reagents, followed by tests of learning and memory abilities and histological staining of the hippocampus. CCK-8 and AnnexinV/PI staining respectively measured the survival and apoptosis rates of primary hippocampal neurons cultured with sevoflurane. The expression levels of miR-34a, SIRT1, p53, Ac-p53, and autophagy- or apoptosis-related proteins were measured. Sevoflurane impaired the learning and memory abilities of mice, increased TUNEL-positive cells in their hippocampus, and hindered the survival of hippocampal neurons. Sevoflurane increased miR-34a, Bax, cleaved caspase-3, and the ratio of LC3-II/LC3-I and reduced SIRT1 and p62. MiR-34a overexpression promoted sevoflurane-induced neural damage, whereas SIRT1 inhibition or p53 upregulation counteracted the neuroprotection of miR-34a knockdown. SIRT1 was a target of miR-34a and promoted p53 deacetylation. MiR-34a promotes sevoflurane-stimulated neuronal apoptosis and autophagy in neonatal mice by inhibiting SIRT1 expression and subsequent p53 deacetylation.