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Dexmedetomidine Post-Conditioning Alleviates Cerebral Ischemia-Reperfusion Injury in Rats by Inhibiting High Mobility Group Protein B1 Group (HMGB1)/Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Signaling Pathway.
Med Sci Monit. 2020 Jan 08; 26:e918617.MS

Abstract

BACKGROUND

Cerebral ischemia-reperfusion injury is a pivotal cause of deaths due to cerebrovascular accident. Increased research efforts are needed to reveal the mechanism underlying its aggravation or alleviation. In this study, the effects of dexmedetomidine post-conditioning on the HMGB1/TLR4/NF-kappaB signaling pathway in cerebral ischemia-reperfusion rats was explored. MATERIAL AND

METHODS

Ninety rats were randomly divided into 5 groups - a sham group (Sham), a model group (I/R), a dexmedetomidine post-conditioning group (Dex), a recombinant high mobility group protein B1 group (rHMGB1), and a recombinant HMGB1+dexmedetomidine post-conditioning group (rHMGB1+Dex) - with 18 rats in each group. Longa grading, wet-dry weighing, TTC staining, HE staining, and immunohistochemical staining were used to assess brain damage. ELISA, RT-PCR, and Western blot analyses were performed to assess expression of IL-1β, TNF-alpha, IL-6, IL-8, HMGB1, TLR4, and NF-kappaB.

RESULTS

Compared with the I/R group, the neurological function score, brain water content, infarction area, and the number of COX-2- and IBA-1-positive cells in the Dex group were significantly lower, accompanied by downregulated expression of the HMGB1/TLR4/NF-kappaB pathway, alleviated inflammation, and oxidative stress injury in brain tissue. These trends were mostly reversed in the rHMGB1 group and rHMGB1+Dex group, but not in the Dex group. Furthermore, when compared to the Dex group, there were significant increases of H₂O₂, MDA, NO, IL-1β, TNF-alpha, IL-6, IL-8, HMGB1, TLR4, and p-P65 in the rHMGB1 group and rHMGB1+Dex group, in which a significant decrease of T-AOC, SOD, and p-IkappaBalpha was also detected.

CONCLUSIONS

Dexmedetomidine post-conditioning can alleviate cerebral ischemia-reperfusion injury in rats by inhibiting the HMGB1/TLR4/NF-kappaB signaling pathway.

Authors+Show Affiliations

Department of Rehabilitation, Linzi District People's Hospital, Zibo, Shandong, China (mainland).Department of Anesthesiology, Yantaishan Hospital, Yantai, Shandong, China (mainland).Department of Obstetrics, Yantaishan Hospital, Yantai, Shandong, China (mainland).Department of Anesthesiology, The Second Hospital of Shandong University, Jinan, Shandong, China (mainland).Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China (mainland).Department of Pain, Jinan Central Hospital affiliated to Shandong University, Jinan, Shandong, China (mainland).Department of Anesthesiology, Haiyang People's Hospital, Haiyang, Shandong, China (mainland).

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31912804

Citation

Zhai, Yongyi, et al. "Dexmedetomidine Post-Conditioning Alleviates Cerebral Ischemia-Reperfusion Injury in Rats By Inhibiting High Mobility Group Protein B1 Group (HMGB1)/Toll-Like Receptor 4 (TLR4)/Nuclear Factor Kappa B (NF-κB) Signaling Pathway." Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, vol. 26, 2020, pp. e918617.
Zhai Y, Zhu Y, Liu J, et al. Dexmedetomidine Post-Conditioning Alleviates Cerebral Ischemia-Reperfusion Injury in Rats by Inhibiting High Mobility Group Protein B1 Group (HMGB1)/Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Signaling Pathway. Med Sci Monit. 2020;26:e918617.
Zhai, Y., Zhu, Y., Liu, J., Xie, K., Yu, J., Yu, L., & Deng, H. (2020). Dexmedetomidine Post-Conditioning Alleviates Cerebral Ischemia-Reperfusion Injury in Rats by Inhibiting High Mobility Group Protein B1 Group (HMGB1)/Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Signaling Pathway. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 26, e918617. https://doi.org/10.12659/MSM.918617
Zhai Y, et al. Dexmedetomidine Post-Conditioning Alleviates Cerebral Ischemia-Reperfusion Injury in Rats By Inhibiting High Mobility Group Protein B1 Group (HMGB1)/Toll-Like Receptor 4 (TLR4)/Nuclear Factor Kappa B (NF-κB) Signaling Pathway. Med Sci Monit. 2020 Jan 8;26:e918617. PubMed PMID: 31912804.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dexmedetomidine Post-Conditioning Alleviates Cerebral Ischemia-Reperfusion Injury in Rats by Inhibiting High Mobility Group Protein B1 Group (HMGB1)/Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Signaling Pathway. AU - Zhai,Yongyi, AU - Zhu,Yulin, AU - Liu,Jingying, AU - Xie,Kun, AU - Yu,Jingui, AU - Yu,Lingzhi, AU - Deng,Hongyan, Y1 - 2020/01/08/ PY - 2020/1/9/entrez PY - 2020/1/9/pubmed PY - 2020/9/30/medline SP - e918617 EP - e918617 JF - Medical science monitor : international medical journal of experimental and clinical research JO - Med Sci Monit VL - 26 N2 - BACKGROUND Cerebral ischemia-reperfusion injury is a pivotal cause of deaths due to cerebrovascular accident. Increased research efforts are needed to reveal the mechanism underlying its aggravation or alleviation. In this study, the effects of dexmedetomidine post-conditioning on the HMGB1/TLR4/NF-kappaB signaling pathway in cerebral ischemia-reperfusion rats was explored. MATERIAL AND METHODS Ninety rats were randomly divided into 5 groups - a sham group (Sham), a model group (I/R), a dexmedetomidine post-conditioning group (Dex), a recombinant high mobility group protein B1 group (rHMGB1), and a recombinant HMGB1+dexmedetomidine post-conditioning group (rHMGB1+Dex) - with 18 rats in each group. Longa grading, wet-dry weighing, TTC staining, HE staining, and immunohistochemical staining were used to assess brain damage. ELISA, RT-PCR, and Western blot analyses were performed to assess expression of IL-1β, TNF-alpha, IL-6, IL-8, HMGB1, TLR4, and NF-kappaB. RESULTS Compared with the I/R group, the neurological function score, brain water content, infarction area, and the number of COX-2- and IBA-1-positive cells in the Dex group were significantly lower, accompanied by downregulated expression of the HMGB1/TLR4/NF-kappaB pathway, alleviated inflammation, and oxidative stress injury in brain tissue. These trends were mostly reversed in the rHMGB1 group and rHMGB1+Dex group, but not in the Dex group. Furthermore, when compared to the Dex group, there were significant increases of H₂O₂, MDA, NO, IL-1β, TNF-alpha, IL-6, IL-8, HMGB1, TLR4, and p-P65 in the rHMGB1 group and rHMGB1+Dex group, in which a significant decrease of T-AOC, SOD, and p-IkappaBalpha was also detected. CONCLUSIONS Dexmedetomidine post-conditioning can alleviate cerebral ischemia-reperfusion injury in rats by inhibiting the HMGB1/TLR4/NF-kappaB signaling pathway. SN - 1643-3750 UR - https://www.unboundmedicine.com/medline/citation/31912804/Dexmedetomidine_Post_Conditioning_Alleviates_Cerebral_Ischemia_Reperfusion_Injury_in_Rats_by_Inhibiting_High_Mobility_Group_Protein_B1_Group__HMGB1_/Toll_Like_Receptor_4__TLR4_/Nuclear_Factor_kappa_B__NF_κB__Signaling_Pathway_ L2 - https://www.medscimonit.com/download/index/idArt/918617 DB - PRIME DP - Unbound Medicine ER -