Affiliations: [a] Department of Anesthesiology, Tianjin First Center Hospital, Tianjin, China | [b] Department of Anesthesiology, Tianjin Chest Hospital, Tianjin, China | [c] Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin, China
Correspondence:
[*]
Address for correspondence: Wenli Yu, Department of Anesthesiology, Tianjin First Center Hospital, No. 24 Fukang Road, Tianjin 300192, China.
Tel.: +86 022 23627130; Fax: +86 010 85630233; E-mail: [email protected]
Note: [1] Zhun Wang and Dangpei Kou contributed equally in this manuscript, and are listed as co-first author of this manuscript.
Abstract: Background:Due to the lack of efficient neuroprotective therapies, the ischemia-reperfusion (I/R) injury is a major medical problem urgently needed to be further studied. Objective:To investigate the neuro-protective effects of propofol-dexmedetomidine (dex) combination on I/R-induced cerebral injury and potential mechanisms. Methods:Sprague-Dawley rats were randomized to sham-operated, I/R, I/R plus propofol, I/R plus dex, and I/R plus propofol-dex combination group. I/R insult was induced by 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion; Drugs were administered 20 min before the onset of ischemia and continued for another 2 h. Functional outcomes, the expression of Superoxide dismutase (SOD), Methane Dicarboxylic Aldehyde (MDA), Tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), caspase-3 and protein kinase B (AKT) were tested. Results:Propofol-dex combination significantly mitigates I/R-induced neurological deficits in model rats compared to dex or propofol infusion alone. The decreased activity of SOD was significantly reversed following co-administration of propofol and dex, along with the down-regulated MDA content. Perioperative treatment with propofol and dex significantly suppressed I/R-up regulated TNF-α and IL-1β expressions, ameliorated AKT1 expression and caspase-3 activity. Conclusion:Propofol-dex combination exerted a stronger neuro-protection against I/R injury when compared with propofol or dex alone.
