Dexmedetomidine alleviates the spinal cord ischemia-reperfusion injury through blocking mast cell degranulation
Jun Ma, Xiao-Long Zhang, Cheng-Yu Wang, Zhi Lin, Jie-Ru Tao, Hua-Cheng Liu, Jun Ma, Xiao-Long Zhang, Cheng-Yu Wang, Zhi Lin, Jie-Ru Tao, Hua-Cheng Liu
Abstract
Objective: To investigate the neuro-protective effects of dexmedetomidine (dex) on I/R-induced spinal injury and potential mechanisms.
Methods: sprague-Dawley rats in the treatment group received intraperitoneal injections of 25 mg/kg dexmedetomidine, MC stabilizer cromolyn (100 mg/kg), MCs stimuliser compound 48/80 (80 mg/kg), PBS at 24 h befor IR. Underwent 5 minutes of aortic occlusion via median sternotomy, functional scores were recorded at 12, 24, 36 and 48 hours after reperfusion. Additionally, 3 mice underwent sham surgery with sternotomy and dissection of the aorta and subclavian artery with no occlusion. Spinal cords were examined for protein kinase B (AKT), CREB, and brain-derived neurotrophic factor (BDNF) following treatment alone or ischemia-reperfusion surgery. Collected the serum to observe the expression of pro-inflammation cytokines (TNF-α, INF-γ and IL-1β) and anti-inflammation cytokines (TGF-β, IL-10 and IL-6). Then the MCs were harvested to test the expression surface molecular of FcεR and MCs' degranulation.
Results: Pretreated the rats with dexmedetomidine has higher neurologic function at all time points after I/R injury. We collected the serum of rats then detected the pro-inflammation cytokines TNF-α, INF-γ and IL-1β levels and anti-inflammation cytokinses TGF-β, IL-10 and IL-6 levels, found that the pro-inflammation cytokines of dexmedetomidine group was decreased whereas the anti-inflammation cytokinses was increased. At the same time the protect protein of AKT, CREB and mRNA BDNF were increased. They had the same results with cromolyn group, and opposite with the compound 48/80 group. We pretreated MCs with dexmedetomidine in vitro, and found that the activity surface molecular of MCs was down-regulation, and MCs degranulation was decreased.
Conclusion: We thus demonstrate a possible mechanism by which dexmedetomidine alleviates spinal cord I/R injury through blocking the MCs degranulation.
Keywords: Dexmedetomidine; degranulation; ischemia-reperfusion injury; mast cell.
Figures
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MCs degranulation induced by anti…
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MCs degranulation induced by anti –DNPIgE mAb and DNP-HAS was evaluated by 4-Nitrophenyl…
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Source: PubMed