Cargando…
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....
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784644820733526016 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8813303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT wangkaifang theimprovementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT sunmeiyan theimprovementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT juanzhaodong theimprovementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT zhangjianxin theimprovementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT sunyingui theimprovementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT wangguizhi theimprovementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT wangchunling theimprovementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT liyanjing theimprovementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT kongwenwen theimprovementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT fanlulu theimprovementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT zhangyue theimprovementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT zhaohongxiang theimprovementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT zhaoxiaoyong theimprovementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT wangkaifang improvementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT sunmeiyan improvementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT juanzhaodong improvementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT zhangjianxin improvementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT sunyingui improvementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT wangguizhi improvementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT wangchunling improvementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT liyanjing improvementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT kongwenwen improvementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT fanlulu improvementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT zhangyue improvementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT zhaohongxiang improvementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway AT zhaoxiaoyong improvementofsepsisassociatedencephalopathybyp2x7rinhibitorthroughinhibitingtheomihtra2apoptoticsignalingpathway |