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The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling Pathway

The pathogenesis of sepsis-associated encephalopathy (SAE) involves many aspects, including intracellular peroxidative stress damage, mitochondrial dysfunction, and cell apoptosis. In this study, we mainly explored the influence of P2X7R on the cognitive function of SAE and its molecular mechanism....

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Autores principales: Wang, Kaifang, Sun, Meiyan, Juan, Zhaodong, Zhang, Jianxin, Sun, Yingui, Wang, Guizhi, Wang, Chunling, Li, Yanjing, Kong, Wenwen, Fan, Lulu, Zhang, Yue, Zhao, Hongxiang, Zhao, Xiaoyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8813303/
https://www.ncbi.nlm.nih.gov/pubmed/35126784
http://dx.doi.org/10.1155/2022/3777351
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author Wang, Kaifang
Sun, Meiyan
Juan, Zhaodong
Zhang, Jianxin
Sun, Yingui
Wang, Guizhi
Wang, Chunling
Li, Yanjing
Kong, Wenwen
Fan, Lulu
Zhang, Yue
Zhao, Hongxiang
Zhao, Xiaoyong
author_facet Wang, Kaifang
Sun, Meiyan
Juan, Zhaodong
Zhang, Jianxin
Sun, Yingui
Wang, Guizhi
Wang, Chunling
Li, Yanjing
Kong, Wenwen
Fan, Lulu
Zhang, Yue
Zhao, Hongxiang
Zhao, Xiaoyong
author_sort Wang, Kaifang
collection PubMed
description The pathogenesis of sepsis-associated encephalopathy (SAE) involves many aspects, including intracellular peroxidative stress damage, mitochondrial dysfunction, and cell apoptosis. In this study, we mainly explored the influence of P2X7R on the cognitive function of SAE and its molecular mechanism. We established a sepsis model using lipopolysaccharide (LPS) stimulation, followed by an assessment of cognitive function using Morris water maze, and then Western Blot was used to analyze the expression of tight junction proteins ZO-1 and Occludin in the hippocampus of mice. TUNEL assay was used to analyze the apoptosis of brain cells in frozen brain slices of mice during sepsis. Human brain microvascular endothelial cells (HBMECs) were used to research the molecular mechanism of brain cell damage induced by P2X7R. The results showed that P2X7R inhibitors dramatically improved the survival rate of mice, relieved the cognitive dysfunction caused by LPS stimulation, and significantly reduced the brain cell apoptosis caused by LPS. In addition, the inhibition of P2X7R can also reduce the production and accumulation of reactive oxygen species (ROS) in HBMECs in vitro and inhibit the apoptosis signaling pathway associated with mitochondrial serine protease Omi/HtrA2 in HBMECs in vitro. These results suggest that P2X7R has strong value as a potential target for the treatment of SAE.
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spelling pubmed-88133032022-02-04 The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling Pathway Wang, Kaifang Sun, Meiyan Juan, Zhaodong Zhang, Jianxin Sun, Yingui Wang, Guizhi Wang, Chunling Li, Yanjing Kong, Wenwen Fan, Lulu Zhang, Yue Zhao, Hongxiang Zhao, Xiaoyong Behav Neurol Research Article The pathogenesis of sepsis-associated encephalopathy (SAE) involves many aspects, including intracellular peroxidative stress damage, mitochondrial dysfunction, and cell apoptosis. In this study, we mainly explored the influence of P2X7R on the cognitive function of SAE and its molecular mechanism. We established a sepsis model using lipopolysaccharide (LPS) stimulation, followed by an assessment of cognitive function using Morris water maze, and then Western Blot was used to analyze the expression of tight junction proteins ZO-1 and Occludin in the hippocampus of mice. TUNEL assay was used to analyze the apoptosis of brain cells in frozen brain slices of mice during sepsis. Human brain microvascular endothelial cells (HBMECs) were used to research the molecular mechanism of brain cell damage induced by P2X7R. The results showed that P2X7R inhibitors dramatically improved the survival rate of mice, relieved the cognitive dysfunction caused by LPS stimulation, and significantly reduced the brain cell apoptosis caused by LPS. In addition, the inhibition of P2X7R can also reduce the production and accumulation of reactive oxygen species (ROS) in HBMECs in vitro and inhibit the apoptosis signaling pathway associated with mitochondrial serine protease Omi/HtrA2 in HBMECs in vitro. These results suggest that P2X7R has strong value as a potential target for the treatment of SAE. Hindawi 2022-01-27 /pmc/articles/PMC8813303/ /pubmed/35126784 http://dx.doi.org/10.1155/2022/3777351 Text en Copyright © 2022 Kaifang Wang 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
Wang, Kaifang
Sun, Meiyan
Juan, Zhaodong
Zhang, Jianxin
Sun, Yingui
Wang, Guizhi
Wang, Chunling
Li, Yanjing
Kong, Wenwen
Fan, Lulu
Zhang, Yue
Zhao, Hongxiang
Zhao, Xiaoyong
The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling Pathway
title The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling Pathway
title_full The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling Pathway
title_fullStr The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling Pathway
title_full_unstemmed The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling Pathway
title_short The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling Pathway
title_sort improvement of sepsis-associated encephalopathy by p2x7r inhibitor through inhibiting the omi/htra2 apoptotic signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8813303/
https://www.ncbi.nlm.nih.gov/pubmed/35126784
http://dx.doi.org/10.1155/2022/3777351
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