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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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Behavioural Neurology |
| Online Access: | http://dx.doi.org/10.1155/2022/3777351 |
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| author | Kaifang Wang Meiyan Sun Zhaodong Juan Jianxin Zhang Yingui Sun Guizhi Wang Chunling Wang Yanjing Li Wenwen Kong Lulu Fan Yue Zhang Hongxiang Zhao Xiaoyong Zhao |
| author_facet | Kaifang Wang Meiyan Sun Zhaodong Juan Jianxin Zhang Yingui Sun Guizhi Wang Chunling Wang Yanjing Li Wenwen Kong Lulu Fan Yue Zhang Hongxiang Zhao Xiaoyong Zhao |
| author_sort | Kaifang Wang |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-1a3d95dd581b4dd1ade07183919449df |
| institution | Kabale University |
| issn | 1875-8584 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Behavioural Neurology |
| spelling | doaj-art-1a3d95dd581b4dd1ade07183919449df2025-08-20T03:54:21ZengWileyBehavioural Neurology1875-85842022-01-01202210.1155/2022/3777351The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling PathwayKaifang Wang0Meiyan Sun1Zhaodong Juan2Jianxin Zhang3Yingui Sun4Guizhi Wang5Chunling Wang6Yanjing Li7Wenwen Kong8Lulu Fan9Yue Zhang10Hongxiang Zhao11Xiaoyong Zhao12Shandong Provincial Medicine and Health Key Laboratory of Clinical AnesthesiaShandong Provincial Medicine and Health Key Laboratory of Clinical AnesthesiaShandong Provincial Medicine and Health Key Laboratory of Clinical AnesthesiaDepartment of AnesthesiologyShandong Provincial Medicine and Health Key Laboratory of Clinical AnesthesiaShandong Provincial Medicine and Health Key Laboratory of Clinical AnesthesiaShandong Provincial Medicine and Health Key Laboratory of Clinical AnesthesiaShandong Provincial Medicine and Health Key Laboratory of Clinical AnesthesiaShandong Provincial Medicine and Health Key Laboratory of Clinical AnesthesiaShandong Provincial Medicine and Health Key Laboratory of Clinical AnesthesiaShandong Provincial Medicine and Health Key Laboratory of Clinical AnesthesiaShandong Provincial Medicine and Health Key Laboratory of Clinical AnesthesiaShandong Provincial Medicine and Health Key Laboratory of Clinical AnesthesiaThe 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.http://dx.doi.org/10.1155/2022/3777351 |
| spellingShingle | Kaifang Wang Meiyan Sun Zhaodong Juan Jianxin Zhang Yingui Sun Guizhi Wang Chunling Wang Yanjing Li Wenwen Kong Lulu Fan Yue Zhang Hongxiang Zhao Xiaoyong Zhao The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling Pathway Behavioural Neurology |
| 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 |
| url | http://dx.doi.org/10.1155/2022/3777351 |
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