Abstract
BackgroundCerebral ischemia/reperfusion injury (CIRI) is a complication of surgical procedure associated with high mortality. The protective effect of dexmedetomidine (DEX) on CIRI has been explored in previous works, yet the underlying molecular mechanism remains unclear. Our study explored the protective effect of DEX and its regulatory mechanism on CIRI.MethodsA CIRI rat model was established using middle cerebral artery occlusion (MCAO). Neurological deficit scores for rats received MCAO modeling or DEX treatment were measured. Cerebral infarction area of rats was detected by TTC staining, while damage of neurons in hippocampal regions of rats was determined by hematoxylin-eosin (HE) staining. Apoptosis rate of neurons in hippocampal regions was examined by TUNEL staining. The dual-luciferase assay was performed to detect the binding of microRNA-214 (miR-214) to Rho-associated kinase 1 (ROCK1).ResultsDEX treatment significantly reduced infarction area of MCAO rats and elevated miR-214 expression. Injection of miR-214 inhibitor attenuated the effect of DEX in MCAO rats by increasing the area of cerebral infarction in rats and apoptosis rate of hippocampal neurons. ROCK1 was targeted and negatively regulated by miR-214. The overexpression of ROCK1 led to activation of NF-κB to aggravate CIRI.ConclusionTherapeutic effects of DEX on CIRI was elicited by overexpressing miR-214 and impairing ROCK1 expression and NF-κB activation. Our finding might provide novel insights into the molecular mechanism of DEX in rats with CIRI.
Highlights
Cerebral ischemia/reperfusion injury (CIRI) is a complication of surgical procedure associated with high mortality
DEX ameliorates CIRI in middle cerebral artery occlusion (MCAO) rats To explore the therapeutic effects of DEX on rats with CIRI, we scored the neurological function of rats at 24 h post-MCAO (Fig. 1A)
TTC staining was performed on coronal sections of rats, which showed that the area of cerebral infarction increased in rats with CIRI, and DEX partially reduced infarction area (Fig. 1B)
Summary
Cerebral ischemia/reperfusion injury (CIRI) is a complication of surgical procedure associated with high mortality. The protective effect of dexmedetomidine (DEX) on CIRI has been explored in previous works, yet the underlying molecular mechanism remains unclear. Our study explored the protective effect of DEX and its regulatory mechanism on CIRI. DEX has already been reported to exert protective effects against IRI of various organs, including the heart and the kidney and to be neuroprotective against CIRI in rats, yet the underlying mechanism remains to be elucidated [7]. We postulated that miR-214, ROCK1, and NF-κB may be involved in DEX-mediated protective effects against CIRI in rats. This study was conducted to validate our assumption and to investigate the impacts of DEX-regulated miR-214 as well as the relevant regulatory mechanism on CIRI using Sprague Dawley (SD) rats with middle cerebral artery occlusion (MCAO)
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