Abstract
Dexmedetomidine (DEX), a highly selective alpha2 adrenergic receptor agonist, is a commonly used anesthetic drug in surgical procedures. Previous studies have indicated that DEX exerts neuroprotective effects while the detailed mechanism has not been fully elucidated. Here, we aim to study the role of lncRNA SHNG16 in DEX-induced brain protection and its underlying molecular mechanism. The rats underwent middle cerebral artery occlusion (MCAO) surgery and oxygen–glucose deprivation (OGD)-treated HT22 hippocampal neurons were treated with DEX, respectively. CCK8 was used to evaluate cell viability. sh-SHNG16 as well as miR-10b-5p mimics were transfected into hippocampal neurons to further explore the bio-function of SNHG16 and miR-10b-5p in vitro. Furthermore, the interactions between SHNG16 and miR-10b-5p, miR-10b-5p and BDNF gene were confirmed by dual-luciferase report assay. Our data revealed that DEX attenuated neurological damage of the MCAO rats and also increased the cell viability of the neurons significantly. Besides, expression of SHNG16 and BDNF were both downregulated while miR-10b-5p was upregulated in MCAO brain tissues or OGD treated neurons. DEX inhibited miR-10b-5p expression but increased SHNG16 and BDNF levels with a dosage effect. After transfection with sh-SHNG16 or miR-10b-5p mimics, the expression of BDNF protein was downregulated, accompanied with decreased neuron viability. Dual-luciferase assay showed that SHNG16 targeted on miR-10b-5p, which also could bind directly to the 3′-UTR sites of BDNF and negatively regulate its expression. In conclusion, DEX exerts neuroprotective in ischemic stroke via improving neuron damage, the underlying mechanism may be upregulating SHNG16 and BDNF via sponging miR-10b-5p.
Highlights
Ischemic cerebrovascular disease remains one of the diseases with the highest morbidity, disability, and mortality in the world, which has been a serious threat to the health and quality of life of the middle-aged and elderly people [1]
Immunohistochemistry of Caspase-3 was used to detect the apoptosis of neurons in the brain, and the results showed that cerebral ischemia significantly increased the number of Caspase-3 labeled neurons, while DEX notably inhibited the number of Caspase-3 positive cells, and the inhibitory effect was
The results showed that cerebral ischemia considerably inhibited the expression of SNHG16 and brain-derived neurotrophic factor (BDNF) but promoted the expression of miR-10b-5p compared with the control group (Fig. 2a–c) in the rat model
Summary
Ischemic cerebrovascular disease remains one of the diseases with the highest morbidity, disability, and mortality in the world, which has been a serious threat to the health and quality of life of the middle-aged and elderly people [1]. From the perspective of the pathogenesis involving ischemic injury, cerebral blood supply disorder is a crucial factor leading to ischemia, hypoxia, and focal ischemic necrosis of brain tissues. Dexmedetomidine (DEX), a new highly selective alpha adrenergic receptor agonist, has been found to have pharmacological properties, such as analgesia, inhibition of sympathetic activity with a dose-dependent effect but without respiratory depression [5]. A large number of in vivo and in vitro studies have shown that DEX can exert neuroprotective effects through a variety of mechanisms. DEX can increase the expression of brain-derived neurotrophic factor (BDNF) in astroglia cells through ERKdependent pathway, thereby diminishing neuronal death caused by glutamate agonists [6]. DEX can reduce the neurotoxicity of neonatal rats mediated by
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