Dexmedetomidine attenuates neuronal injury after spinal cord ischaemia-reperfusion injury by targeting the CNPY2-endoplasmic reticulum stress signalling.

J Cell Mol Med

Department of Anaesthesiology, Central Laboratory, Tianjin 4th Centre Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin, China.

Published: December 2019

Dexmedetomidine (Dex) has been proven to exert protective effects on multiple organs in response to ischaemia-reperfusion injury, but the specific mechanism by which this occurs has not been fully elucidated. The purpose of this study was to investigate whether Dex attenuates spinal cord ischaemia-reperfusion injury (SCIRI) by inhibiting endoplasmic reticulum stress (ERS). Our team established a model of SCIRI and utilized the endoplasmic reticulum agonist thapsigargin. Dex (25 g/kg) was intraperitoneally injected 30 minutes before spinal cord ischaemia. After 45 minutes of ischaemia, the spinal cord was reperfused for 24 hours. To evaluate the neuroprotective effect of Dex on SCIRI, neurological function scores were assessed in rats and apoptosis of spinal cord cells was determined by TUNEL staining. To determine whether the endoplasmic reticulum apoptosis pathway CNPY2-PERK was involved in the neuroprotective mechanism of Dex, the expression levels of related proteins (CNPY2, GRP78, PERK, CHOP, caspase-12, caspase-9 and caspase-3) were detected by western blot analysis and RT-PCR. We observed that Dex significantly increased the neurological function scores after SCIRI and decreased apoptosis of spinal cord cells. The expression of ERS-related apoptosis proteins was significantly increased by SCIRI but was significantly decreased in response to Dex administration. Taken together, the results of this study indicate that Dex may attenuate SCIRI by inhibiting the CNPY2-ERS apoptotic pathway.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850922PMC
http://dx.doi.org/10.1111/jcmm.14688DOI Listing

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