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The role of Wnt/β-catenin pathway in the protection process by dexmedetomidine against cerebral ischemia/reperfusion injury in rats.
Life Sci. 2019 Nov 01; 236:116921.LS

Abstract

AIMS

To assess the role of glycogen synthase kinase-3β (GSK3β) and β-catenin in the protection of ischemic injury by dexmedetomidine (Dex).

MAIN METHODS

Adult male Sprague-Dawley rats were subjected to (middle cerebral artery occlusion, MCAO) for 2 h followed by reperfusion and Dex was administered 30min before MCAO. The neurological deficit score, cerebral infarct size and neuron survival were evaluated at 24 h after reperfusion. The expression of pAKT, pGSK3β and β-catenin in the ischemic penumbra was assayed by Western blot at 2 h after reperfusion.

KEY FINDINGS

We found that the Dex-induced increment of neuron survival in the ischemic penumbra was diminished by the PI3K inhibitor LY294002 and the β-catenin inhibitor XAV939, respectively. The increasing expression of pAKT, pGSK3β and β-catenin induced by Dex was markedly inhibited by LY294002. And the increasing expression of β-catenin in nuclei induced by Dex was markedly inhibited by XAV939. At the same time, the GSK3β inhibitor SB216763 also caused an increment of neuron survival and an increasing expression of pGSK3β and β-catenin in the ischemic penumbra.

SIGNIFICANCE

Our data suggested that treatment with Dex reduced cerebral injury in rats exposed to cerebral ischemia-reperfusion (I/R) by the activation of the PI3K/AKT/GSK3β pathways as well the activation of downstream Wnt/β-catenin pathway. And the Wnt/β-catenin pathway may play an important role in the protection against cerebral ischemia/reperfusion injury in rats.

Authors+Show Affiliations

Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, PR China; Department of Anesthesiology, The First Affiliated Hospital of Jingzhou Medical University, Jinzhou, 121001, PR China.Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, PR China.Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, PR China. Electronic address: 18040099898@qq.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31610196

Citation

Li, Ping, et al. "The Role of Wnt/β-catenin Pathway in the Protection Process By Dexmedetomidine Against Cerebral Ischemia/reperfusion Injury in Rats." Life Sciences, vol. 236, 2019, p. 116921.
Li P, Zhang Y, Liu H. The role of Wnt/β-catenin pathway in the protection process by dexmedetomidine against cerebral ischemia/reperfusion injury in rats. Life Sci. 2019;236:116921.
Li, P., Zhang, Y., & Liu, H. (2019). The role of Wnt/β-catenin pathway in the protection process by dexmedetomidine against cerebral ischemia/reperfusion injury in rats. Life Sciences, 236, 116921. https://doi.org/10.1016/j.lfs.2019.116921
Li P, Zhang Y, Liu H. The Role of Wnt/β-catenin Pathway in the Protection Process By Dexmedetomidine Against Cerebral Ischemia/reperfusion Injury in Rats. Life Sci. 2019 Nov 1;236:116921. PubMed PMID: 31610196.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of Wnt/β-catenin pathway in the protection process by dexmedetomidine against cerebral ischemia/reperfusion injury in rats. AU - Li,Ping, AU - Zhang,Yongfang, AU - Liu,Hongtao, Y1 - 2019/10/11/ PY - 2019/07/07/received PY - 2019/09/26/revised PY - 2019/09/27/accepted PY - 2019/10/15/pubmed PY - 2019/11/9/medline PY - 2019/10/15/entrez KW - Dexmedetomidine KW - GSK-3β KW - Ischemia/reperfusion injury KW - PI3K/AKT KW - Wnt/β-catenin SP - 116921 EP - 116921 JF - Life sciences JO - Life Sci. VL - 236 N2 - AIMS: To assess the role of glycogen synthase kinase-3β (GSK3β) and β-catenin in the protection of ischemic injury by dexmedetomidine (Dex). MAIN METHODS: Adult male Sprague-Dawley rats were subjected to (middle cerebral artery occlusion, MCAO) for 2 h followed by reperfusion and Dex was administered 30min before MCAO. The neurological deficit score, cerebral infarct size and neuron survival were evaluated at 24 h after reperfusion. The expression of pAKT, pGSK3β and β-catenin in the ischemic penumbra was assayed by Western blot at 2 h after reperfusion. KEY FINDINGS: We found that the Dex-induced increment of neuron survival in the ischemic penumbra was diminished by the PI3K inhibitor LY294002 and the β-catenin inhibitor XAV939, respectively. The increasing expression of pAKT, pGSK3β and β-catenin induced by Dex was markedly inhibited by LY294002. And the increasing expression of β-catenin in nuclei induced by Dex was markedly inhibited by XAV939. At the same time, the GSK3β inhibitor SB216763 also caused an increment of neuron survival and an increasing expression of pGSK3β and β-catenin in the ischemic penumbra. SIGNIFICANCE: Our data suggested that treatment with Dex reduced cerebral injury in rats exposed to cerebral ischemia-reperfusion (I/R) by the activation of the PI3K/AKT/GSK3β pathways as well the activation of downstream Wnt/β-catenin pathway. And the Wnt/β-catenin pathway may play an important role in the protection against cerebral ischemia/reperfusion injury in rats. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/31610196/The_role_of_Wnt/β_catenin_pathway_in_the_protection_process_by_dexmedetomidine_against_cerebral_ischemia/reperfusion_injury_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(19)30848-3 DB - PRIME DP - Unbound Medicine ER -