Background:
Dexmedetomidine (Dex) is widely used in perioperative anesthesia, and
recent studies have reported that it protects organs from ischemia/reperfusion (I/R) injury.
Objective:
This study was performed to investigate the role of Dex in alleviating cerebral I/R injury and its regulatory effects on metastasis-associated lung adenocarcinoma transcript 1
(MALAT1)/microRNA-140-5p (miR-140-5p)/nuclear factor erythroid-derived 2-like 2 (Nrf2)
axis.
Methods:
In vivo rat middle cerebral artery occlusion (MCAO) model and in vitro oxygen-glucose
deprivation/re-oxygenation (OGD/R)-induced neuronal injury model were constructed. Dex was
injected into the animals or used to culture HT22 cells to observe the pharmacological effects. The
neurological defect, brain water content, infarct volume of the rats, and neuron viability were evaluated. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were detected. Besides, the regulatory effects of Dex on
MALAT1, miR-140-5p, and Nrf2 expression levels and regulatory relationships among them were
evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and dual-luciferase reporter assay.
Results:
Dex significantly alleviated the neurological injury of rats with MCAO and promoted the
viability of neurons. Dex treatment suppressed miR-140-5p expression, but elevated MALAT1
and Nrf2 expressions. MALAT1 knockdown down-regulated Nrf2 expression and promoted oxidative stress in neurons. Additionally, miR-140-5p directly targeted Nrf2, and it also functioned as a
downstream target miRNA of MALAT1.
Conclusion:
Dex, via regulating MALAT1/miR-140-5p/Nrf2 axis, plays a neuroprotective role
against I/R-induced brain injury.