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To investigate the role and mechanism of microRNA-124-3p (miR-124-3p) and serine palmitoyltransferase long chain base subunit 2 (SPTLC2) in neuronal apoptosis induced by mechanical injury. Transient transfection was used to modify the expression of miR-124-3p and SPTLC2. After transfection, neuronal apoptosis was evaluated in an in vitro injury model of primary neurons using TUNEL staining and western blot. The correlation between miR-124-3p and SPTLC2 was identified through a dual luciferase reporter assay in HEK293 cells. A rescue experiment in primary neurons was performed to further confirm the result. To explore the downstream mechanisms, co-immunoprecipitation was performed to identify proteins that interact with SPTLC2 in toll-like receptor 4 (TLR4) signalling pathway. Subsequently, the relative expression levels of TLR4 pathway molecules were measured by western blot. Our results showed that increased miR-124-3p can inhibit neuronal apoptosis, which is opposite to the effect of SPTLC2. In addition, miR-124-3p was proved to negatively regulate SPTLC2 expression and suppress the apoptosis-promoting effect of SPTLC2 via the TLR4 signalling pathway.
相似文献Mitochondrial dysfunction has been proposed to be one of the earliest triggering events in isoflurane-induced neuronal damage. Lidocaine has been demonstrated to attenuate the impairment of cognition in aged rats induced by isoflurane in our previous study. In this study, we hypothesized that lidocaine could attenuate isoflurane anesthesia-induced cognitive impairment by reducing mitochondrial damage. H4 human neuroglioma cells and 18-month-old male Fischer 344 rats were exposed to isoflurane or isoflurane plus lidocaine. Cognitive function was tested at 14 days after treatment by the Barnes Maze test in male Fischer 344 rats. Morphology was observed under electron microscope, and mitochondrial transmembrane potential, electron transfer chain (ETC) enzyme activity, complex-I–IV activity, immunofluorescence and flow cytometry of annexin V-FITC binding, TUNEL assay, and Western blot analyses were applied. Lidocaine attenuated cognitive impairment caused by isoflurane in aged Fischer 344 rat. Lidocaine was effective in reducing mitochondrial damage, mitigating the decrease in mitochondrial membrane potential (ΔΨm), reversing isoflurane-induced changes in complex activity in the mitochondrial electron transfer chain and inhibiting the apoptotic activities induced by isoflurane in H4 cells and Fischer 344 rats. Additionally, lidocaine suppressed the ratio of Bax (the apoptosis-promoting protein) to Bcl-2 (the apoptosis-inhibiting protein) caused by isoflurane in H4 cells. Lidocaine proved effective in attenuating isoflurane-induced POCD by reducing mitochondrial damage.
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