3-Hydroxybutyrate alleviates septic liver injury by promoting macrophage polarization from M1 to M2
Objective To investigate the therapeutic effects and underlying mechanisms of the metabolite 3- hydroxybutyrate (3HB) in a cecal ligation and puncture (CLP)-induced sepsis model in mice. Methods Male C57BL / 6J mice were divided into three groups: Sham, CLP, and CLP + 3HB groups. The survival rate,...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | zho |
| Published: |
Lanzhou University Press
2024-12-01
|
| Series: | 生物医学转化 |
| Subjects: | |
| Online Access: | http://swyxzh.ijournals.cn/swyxzh/article/html/20240403 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841543709905125376 |
|---|---|
| author | Hu Jingjuan Deng Fan Sun Qishun Min Yue Feng Siyuan Wu Ling Chen Xiaofeng Liu Kexuan |
| author_facet | Hu Jingjuan Deng Fan Sun Qishun Min Yue Feng Siyuan Wu Ling Chen Xiaofeng Liu Kexuan |
| author_sort | Hu Jingjuan |
| collection | DOAJ |
| description | Objective To investigate the therapeutic effects and underlying mechanisms of the metabolite 3- hydroxybutyrate (3HB) in a cecal ligation and puncture (CLP)-induced sepsis model in mice. Methods Male C57BL / 6J mice were divided into three groups: Sham, CLP, and CLP + 3HB groups. The survival rate, liver histopathological damage, serum levels of Alanine Transaminase(ALT) and Aspartate Aminotransferase(AST), and hepatic mRNA expression of inflammatory cytokines IL-1β and IL-6 were evaluated. Subsequently, macrophages were depleted using clodronate liposomes (Clo-Lipro) to explore their role in 3HB treatment. Male C57BL/6J mice were divided into five groups: CLP, CLP+3HB, CLP+ PBS-Lipro, CLP+Clo-Lipro, and CLP+ 3HB + Clo-Lipro. Peritoneal macrophage polarization (M1 and M2 phenotypes), liver injury, and inflammatory cytokine expression were analyzed. Results Treatment with 3HB significantly improved the survival rate of septic mice, alleviated liver injury, and reduced levels of ALT, AST, IL-1β, and IL-6. 3HB promoted the polarization of macrophages from M1 to the M2 phenotype in septic mice, while macrophage depletion exacerbated liver injury in septic mice and reversed the protective effects of 3HB. Conclusion 3HB alleviates septic liver injury by promoting macrophage polarization from M1 to M2. This effect is dependent on the participation of macrophages, providing new insights and potential intervention strategies for the clinical treatment of septic liver injury. |
| format | Article |
| id | doaj-art-9e6c39b3b6d3457595a49ce2cade69ac |
| institution | Kabale University |
| issn | 2096-8965 |
| language | zho |
| publishDate | 2024-12-01 |
| publisher | Lanzhou University Press |
| record_format | Article |
| series | 生物医学转化 |
| spelling | doaj-art-9e6c39b3b6d3457595a49ce2cade69ac2025-01-13T07:56:16ZzhoLanzhou University Press生物医学转化2096-89652024-12-0154222710.12287/j.issn.2096-8965.202404033-Hydroxybutyrate alleviates septic liver injury by promoting macrophage polarization from M1 to M2Hu Jingjuan0Deng Fan1Sun Qishun2Min Yue3Feng Siyuan4Wu Ling5Chen Xiaofeng6Liu Kexuan7Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 , Guangdong, China ；The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou 510515 , Guangdong, ChinaDepartment of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 , Guangdong, China ；The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou 510515 , Guangdong, ChinaDepartment of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 , Guangdong, China ；The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou 510515 , Guangdong, ChinaDepartment of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 , Guangdong, China ；The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou 510515 , Guangdong, ChinaDepartment of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 , Guangdong, China ；The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou 510515 , Guangdong, ChinaDepartment of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 , Guangdong, China ；The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou 510515 , Guangdong, ChinaDepartment of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 , Guangdong, China ；The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou 510515 , Guangdong, ChinaDepartment of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 , Guangdong, China ；The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou 510515 , Guangdong, ChinaObjective To investigate the therapeutic effects and underlying mechanisms of the metabolite 3- hydroxybutyrate (3HB) in a cecal ligation and puncture (CLP)-induced sepsis model in mice. Methods Male C57BL / 6J mice were divided into three groups: Sham, CLP, and CLP + 3HB groups. The survival rate, liver histopathological damage, serum levels of Alanine Transaminase(ALT) and Aspartate Aminotransferase(AST), and hepatic mRNA expression of inflammatory cytokines IL-1β and IL-6 were evaluated. Subsequently, macrophages were depleted using clodronate liposomes (Clo-Lipro) to explore their role in 3HB treatment. Male C57BL/6J mice were divided into five groups: CLP, CLP+3HB, CLP+ PBS-Lipro, CLP+Clo-Lipro, and CLP+ 3HB + Clo-Lipro. Peritoneal macrophage polarization (M1 and M2 phenotypes), liver injury, and inflammatory cytokine expression were analyzed. Results Treatment with 3HB significantly improved the survival rate of septic mice, alleviated liver injury, and reduced levels of ALT, AST, IL-1β, and IL-6. 3HB promoted the polarization of macrophages from M1 to the M2 phenotype in septic mice, while macrophage depletion exacerbated liver injury in septic mice and reversed the protective effects of 3HB. Conclusion 3HB alleviates septic liver injury by promoting macrophage polarization from M1 to M2. This effect is dependent on the participation of macrophages, providing new insights and potential intervention strategies for the clinical treatment of septic liver injury.http://swyxzh.ijournals.cn/swyxzh/article/html/20240403sepsis liver injury3-hydroxybutyratemacrophage polarization |
| spellingShingle | Hu Jingjuan Deng Fan Sun Qishun Min Yue Feng Siyuan Wu Ling Chen Xiaofeng Liu Kexuan 3-Hydroxybutyrate alleviates septic liver injury by promoting macrophage polarization from M1 to M2 生物医学转化 sepsis liver injury 3-hydroxybutyrate macrophage polarization |
| title | 3-Hydroxybutyrate alleviates septic liver injury by promoting macrophage polarization from M1 to M2 |
| title_full | 3-Hydroxybutyrate alleviates septic liver injury by promoting macrophage polarization from M1 to M2 |
| title_fullStr | 3-Hydroxybutyrate alleviates septic liver injury by promoting macrophage polarization from M1 to M2 |
| title_full_unstemmed | 3-Hydroxybutyrate alleviates septic liver injury by promoting macrophage polarization from M1 to M2 |
| title_short | 3-Hydroxybutyrate alleviates septic liver injury by promoting macrophage polarization from M1 to M2 |
| title_sort | 3 hydroxybutyrate alleviates septic liver injury by promoting macrophage polarization from m1 to m2 |
| topic | sepsis liver injury 3-hydroxybutyrate macrophage polarization |
| url | http://swyxzh.ijournals.cn/swyxzh/article/html/20240403 |
| work_keys_str_mv | AT hujingjuan 3hydroxybutyratealleviatessepticliverinjurybypromotingmacrophagepolarizationfromm1tom2 AT dengfan 3hydroxybutyratealleviatessepticliverinjurybypromotingmacrophagepolarizationfromm1tom2 AT sunqishun 3hydroxybutyratealleviatessepticliverinjurybypromotingmacrophagepolarizationfromm1tom2 AT minyue 3hydroxybutyratealleviatessepticliverinjurybypromotingmacrophagepolarizationfromm1tom2 AT fengsiyuan 3hydroxybutyratealleviatessepticliverinjurybypromotingmacrophagepolarizationfromm1tom2 AT wuling 3hydroxybutyratealleviatessepticliverinjurybypromotingmacrophagepolarizationfromm1tom2 AT chenxiaofeng 3hydroxybutyratealleviatessepticliverinjurybypromotingmacrophagepolarizationfromm1tom2 AT liukexuan 3hydroxybutyratealleviatessepticliverinjurybypromotingmacrophagepolarizationfromm1tom2 |