Cargando…
Xuesaitong Combined with Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats by Activating Keap1/Nrf2 Signaling and Mitophagy in Hippocampal Tissue
Ischemic stroke is the most common type of cerebrovascular disease with high mortality and poor prognosis, and cerebral ischemia-reperfusion (CI/R) injury is the main murderer. Here, we attempted to explore the effects and mechanism of Xuesaitong (XST) combined with dexmedetomidine (Dex) on CI/R inj...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9750788/ https://www.ncbi.nlm.nih.gov/pubmed/36531207 http://dx.doi.org/10.1155/2022/5126042 |
_version_ | 1784850334444683264 |
---|---|
author | Han, Guo-Jie Min, Xiang-Zhen Ma, Shuang-Shuang Ding, Chuan Wang, Xiu-Qin |
author_facet | Han, Guo-Jie Min, Xiang-Zhen Ma, Shuang-Shuang Ding, Chuan Wang, Xiu-Qin |
author_sort | Han, Guo-Jie |
collection | PubMed |
description | Ischemic stroke is the most common type of cerebrovascular disease with high mortality and poor prognosis, and cerebral ischemia-reperfusion (CI/R) injury is the main murderer. Here, we attempted to explore the effects and mechanism of Xuesaitong (XST) combined with dexmedetomidine (Dex) on CI/R injury in rats. First, a rat model of CI/R injury was constructed via the middle cerebral artery occlusion (MCAO) method and treated with XST and Dex alone or in combination. Then, on the 5th and 10th days of treatment, the neurological impairment was assessed using the modified neurological severity scores (mNSS), the 8-arm radial maze test (8ARMT), novel object recognition test (NORT), and fear conditioning test (FCT). H&E staining was performed to observe the pathological changes of the hippocampus. ELISA and related kits were used to assess the monoamine neurotransmitters and antioxidant enzyme activities in the hippocampus. The ATP, mitochondrial membrane potential levels, and qRT-PCR of genes related to mitochondrial function were determined to assess mitochondrial functions in the hippocampus and western blot to determine Keap1/Nrf2 signaling pathway and mitophagy-related protein expression. The results showed that XST combined with Dex significantly reduced mNSS, improved spatial memory and learning deficits, and enhanced fear memory and cognitive memory ability in CI/R rats, which was superior to single-drug treatment. Moreover, XST combined with Dex treatment improved hippocampal histopathological damage; significantly increased the levels of monoamine neurotransmitters, neurotrophic factors, ATP, and mitochondrial membrane potential; and upregulated the activities of antioxidant enzymes and the expression of mitophagy-related proteins in the hippocampus of CI/R rats. XST combined with Dex treatment also activated the Keap1/Nrf2 signaling and upregulated the protein expression of downstream antioxidant enzymes HO-1 and NQ. Altogether, this study showed that a combination of XST and Dex could activate the Keap1/Nrf2 signaling and mitophagy to protect rats from CI/R-related neurological impairment. |
format | Online Article Text |
id | pubmed-9750788 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-97507882022-12-15 Xuesaitong Combined with Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats by Activating Keap1/Nrf2 Signaling and Mitophagy in Hippocampal Tissue Han, Guo-Jie Min, Xiang-Zhen Ma, Shuang-Shuang Ding, Chuan Wang, Xiu-Qin Oxid Med Cell Longev Research Article Ischemic stroke is the most common type of cerebrovascular disease with high mortality and poor prognosis, and cerebral ischemia-reperfusion (CI/R) injury is the main murderer. Here, we attempted to explore the effects and mechanism of Xuesaitong (XST) combined with dexmedetomidine (Dex) on CI/R injury in rats. First, a rat model of CI/R injury was constructed via the middle cerebral artery occlusion (MCAO) method and treated with XST and Dex alone or in combination. Then, on the 5th and 10th days of treatment, the neurological impairment was assessed using the modified neurological severity scores (mNSS), the 8-arm radial maze test (8ARMT), novel object recognition test (NORT), and fear conditioning test (FCT). H&E staining was performed to observe the pathological changes of the hippocampus. ELISA and related kits were used to assess the monoamine neurotransmitters and antioxidant enzyme activities in the hippocampus. The ATP, mitochondrial membrane potential levels, and qRT-PCR of genes related to mitochondrial function were determined to assess mitochondrial functions in the hippocampus and western blot to determine Keap1/Nrf2 signaling pathway and mitophagy-related protein expression. The results showed that XST combined with Dex significantly reduced mNSS, improved spatial memory and learning deficits, and enhanced fear memory and cognitive memory ability in CI/R rats, which was superior to single-drug treatment. Moreover, XST combined with Dex treatment improved hippocampal histopathological damage; significantly increased the levels of monoamine neurotransmitters, neurotrophic factors, ATP, and mitochondrial membrane potential; and upregulated the activities of antioxidant enzymes and the expression of mitophagy-related proteins in the hippocampus of CI/R rats. XST combined with Dex treatment also activated the Keap1/Nrf2 signaling and upregulated the protein expression of downstream antioxidant enzymes HO-1 and NQ. Altogether, this study showed that a combination of XST and Dex could activate the Keap1/Nrf2 signaling and mitophagy to protect rats from CI/R-related neurological impairment. Hindawi 2022-12-07 /pmc/articles/PMC9750788/ /pubmed/36531207 http://dx.doi.org/10.1155/2022/5126042 Text en Copyright © 2022 Guo-Jie Han et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Han, Guo-Jie Min, Xiang-Zhen Ma, Shuang-Shuang Ding, Chuan Wang, Xiu-Qin Xuesaitong Combined with Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats by Activating Keap1/Nrf2 Signaling and Mitophagy in Hippocampal Tissue |
title | Xuesaitong Combined with Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats by Activating Keap1/Nrf2 Signaling and Mitophagy in Hippocampal Tissue |
title_full | Xuesaitong Combined with Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats by Activating Keap1/Nrf2 Signaling and Mitophagy in Hippocampal Tissue |
title_fullStr | Xuesaitong Combined with Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats by Activating Keap1/Nrf2 Signaling and Mitophagy in Hippocampal Tissue |
title_full_unstemmed | Xuesaitong Combined with Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats by Activating Keap1/Nrf2 Signaling and Mitophagy in Hippocampal Tissue |
title_short | Xuesaitong Combined with Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats by Activating Keap1/Nrf2 Signaling and Mitophagy in Hippocampal Tissue |
title_sort | xuesaitong combined with dexmedetomidine improves cerebral ischemia-reperfusion injury in rats by activating keap1/nrf2 signaling and mitophagy in hippocampal tissue |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9750788/ https://www.ncbi.nlm.nih.gov/pubmed/36531207 http://dx.doi.org/10.1155/2022/5126042 |
work_keys_str_mv | AT hanguojie xuesaitongcombinedwithdexmedetomidineimprovescerebralischemiareperfusioninjuryinratsbyactivatingkeap1nrf2signalingandmitophagyinhippocampaltissue AT minxiangzhen xuesaitongcombinedwithdexmedetomidineimprovescerebralischemiareperfusioninjuryinratsbyactivatingkeap1nrf2signalingandmitophagyinhippocampaltissue AT mashuangshuang xuesaitongcombinedwithdexmedetomidineimprovescerebralischemiareperfusioninjuryinratsbyactivatingkeap1nrf2signalingandmitophagyinhippocampaltissue AT dingchuan xuesaitongcombinedwithdexmedetomidineimprovescerebralischemiareperfusioninjuryinratsbyactivatingkeap1nrf2signalingandmitophagyinhippocampaltissue AT wangxiuqin xuesaitongcombinedwithdexmedetomidineimprovescerebralischemiareperfusioninjuryinratsbyactivatingkeap1nrf2signalingandmitophagyinhippocampaltissue |