Propofol Downregulates lncRNA MALAT1 to Alleviate Cerebral Ischemia-Reperfusion Injury.

Abstract

Propofol (PPF) is reported to play a protective role in ischemia/reperfusion (I/R) injury, including cerebral ischemia-reperfusion injury (CIRI). This study aims to investigate the mechanism by which PPF ameliorates CIRI. Kunming mice were used to establish the middle cerebral artery occlusion (MCAO)/reperfusion mouse model in vivo. PPF pre-treatment was performed before CIRI. Lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) levels were detected to evaluate the tissue injury. PC12 cells were exposed to hypoxia/reoxygenation (H/R) to construct the in vitro CIRI model, and PC12 cells were pre-treated with PPF before H/R. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression of lncRNA MALAT1 and miR-182-5p. Flow cytometry was used to detect the apoptosis of PC12 cells. Bioinformatics analysis, qRT-PCR, dual-luciferase reporter gene experiments, and RNA immunoprecipitation (RIP) experiments were performed to predict and validate the targeting relationship between MALAT1 and miR-182-5p. Western blot was used to detect Toll-like receptor 4 (TLR4) expression at protein level. PPF pre-treatment remarkably inhibited LDH and CPK levels in the serum of the mice with CIRI, and reduced the apoptosis of PC12 cells exposed to H/R. Besides, PPF pre-treatment markedly suppressed MALAT1 expression in both in vivo and in vitro models and upregulated miR-182-5p expression. MiR-182-5p was validated to be a downstream target gene of MALAT1, and MALAT1 could increase the expression of TLR4 by suppressing miR-182-5p. The effects of PPF on the injury of the mice brain and PC12 cells were partly counteracted by the restoration of MALAT1. PPF protects the brain against I/R-induced injury by regulating MALAT1/miR-182-5p/TLR4 axis.