Dexmedetomidine reduces myocardial ischemia-reperfusion injury in young mice through MIF/AMPK/GLUT4 axis
Abstract Background Reperfusion of ischemic tissue has adverse impact on the myocardium. Dexmedetomidine (Dex) is a α2-adrenergic receptor (α2-AR) agonist with sedative and analgesic effects. Macrophage migration inhibition factor (MIF) is a pressure-regulating cytokine and is responsible for inflam...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | BMC Anesthesiology |
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| Online Access: | https://doi.org/10.1186/s12871-022-01825-z |
| _version_ | 1798036421330599936 |
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| author | Siyu Chen Aimei Li Jianjiang Wu Yidan Huang Tiantian Zou Taiwangu Tailaiti Jiang Wang |
| author_facet | Siyu Chen Aimei Li Jianjiang Wu Yidan Huang Tiantian Zou Taiwangu Tailaiti Jiang Wang |
| author_sort | Siyu Chen |
| collection | DOAJ |
| description | Abstract Background Reperfusion of ischemic tissue has adverse impact on the myocardium. Dexmedetomidine (Dex) is a α2-adrenergic receptor (α2-AR) agonist with sedative and analgesic effects. Macrophage migration inhibition factor (MIF) is a pressure-regulating cytokine and is responsible for inflammatory and immune diseases. This study aims to reveal the consequences of Dex on myocardial ischemia-reperfusion injury (IRI) in young mice. Methods Fifty mice were raised and examined. At the end of the experiment, all mice were euthanized. The anterior descending department of the left coronary artery in mice was under ischemia for 60 min, then the ligation line was released and reperfused for 120 min to establish the IRI model. Mice were randomly divided into Sham, control, treatment using 4,5-dihydro-3-(4-hydroxyphenyl)-5-isoxazoleacetic acid (ISO-1), Dex treatment, and Dex combined ISO-1 treatment groups. Interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) and ATP levels were recorded. The expressions of MIF, P-adenosine monophosphate-activated kinase α (AMPKα), glucose transporter (GLUT)4, Bax and Bcl-2 were detected by Western Blot (WB). Hematoxylin and Eosin (H&E) staining was used to study cell morphology. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Echocardiography was carried out at the end of reperfusion, and the infarct size was calculated by Electron microscopy. Results I/R + Dex group showed significantly increased IL-6 and TNF-α levels and reduced myocardial cell necrosis and apoptosis. H&E staining showed alleviated myocardial disorder, myocardial cell swelling, myocardial fiber fracture, and inflammatory cell infiltration in I/R + Dex group. Myocardial cell necrosis and apoptosis were significantly reduced in I/R + Dex group. ATP level in myocardial tissue of mice in I/R group was substantially decreased, while that in Dex group was increased. WB results showed that MIF, P-AMPK α, GLUT4 and Bcl-2 levels were increased and Bax levels were decreased in I/R + Dex group. Conclusion Dex may exert myocardial protection in young mice through MIF/AMPK/GLUT4 axis. |
| first_indexed | 2024-04-11T21:12:44Z |
| format | Article |
| id | doaj.art-2d26d56031874b6e9795905de44bc4f0 |
| institution | Directory Open Access Journal |
| issn | 1471-2253 |
| language | English |
| last_indexed | 2024-04-11T21:12:44Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Anesthesiology |
| spelling | doaj.art-2d26d56031874b6e9795905de44bc4f02022-12-22T04:02:56ZengBMCBMC Anesthesiology1471-22532022-09-012211910.1186/s12871-022-01825-zDexmedetomidine reduces myocardial ischemia-reperfusion injury in young mice through MIF/AMPK/GLUT4 axisSiyu Chen0Aimei Li1Jianjiang Wu2Yidan Huang3Tiantian Zou4Taiwangu Tailaiti5Jiang Wang6Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical UniversityAbstract Background Reperfusion of ischemic tissue has adverse impact on the myocardium. Dexmedetomidine (Dex) is a α2-adrenergic receptor (α2-AR) agonist with sedative and analgesic effects. Macrophage migration inhibition factor (MIF) is a pressure-regulating cytokine and is responsible for inflammatory and immune diseases. This study aims to reveal the consequences of Dex on myocardial ischemia-reperfusion injury (IRI) in young mice. Methods Fifty mice were raised and examined. At the end of the experiment, all mice were euthanized. The anterior descending department of the left coronary artery in mice was under ischemia for 60 min, then the ligation line was released and reperfused for 120 min to establish the IRI model. Mice were randomly divided into Sham, control, treatment using 4,5-dihydro-3-(4-hydroxyphenyl)-5-isoxazoleacetic acid (ISO-1), Dex treatment, and Dex combined ISO-1 treatment groups. Interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) and ATP levels were recorded. The expressions of MIF, P-adenosine monophosphate-activated kinase α (AMPKα), glucose transporter (GLUT)4, Bax and Bcl-2 were detected by Western Blot (WB). Hematoxylin and Eosin (H&E) staining was used to study cell morphology. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Echocardiography was carried out at the end of reperfusion, and the infarct size was calculated by Electron microscopy. Results I/R + Dex group showed significantly increased IL-6 and TNF-α levels and reduced myocardial cell necrosis and apoptosis. H&E staining showed alleviated myocardial disorder, myocardial cell swelling, myocardial fiber fracture, and inflammatory cell infiltration in I/R + Dex group. Myocardial cell necrosis and apoptosis were significantly reduced in I/R + Dex group. ATP level in myocardial tissue of mice in I/R group was substantially decreased, while that in Dex group was increased. WB results showed that MIF, P-AMPK α, GLUT4 and Bcl-2 levels were increased and Bax levels were decreased in I/R + Dex group. Conclusion Dex may exert myocardial protection in young mice through MIF/AMPK/GLUT4 axis.https://doi.org/10.1186/s12871-022-01825-zDexmedetomidine (Dex)MIF/AMPK/GLUT4 axisHeart ischemia-reperfusion injury |
| spellingShingle | Siyu Chen Aimei Li Jianjiang Wu Yidan Huang Tiantian Zou Taiwangu Tailaiti Jiang Wang Dexmedetomidine reduces myocardial ischemia-reperfusion injury in young mice through MIF/AMPK/GLUT4 axis BMC Anesthesiology Dexmedetomidine (Dex) MIF/AMPK/GLUT4 axis Heart ischemia-reperfusion injury |
| title | Dexmedetomidine reduces myocardial ischemia-reperfusion injury in young mice through MIF/AMPK/GLUT4 axis |
| title_full | Dexmedetomidine reduces myocardial ischemia-reperfusion injury in young mice through MIF/AMPK/GLUT4 axis |
| title_fullStr | Dexmedetomidine reduces myocardial ischemia-reperfusion injury in young mice through MIF/AMPK/GLUT4 axis |
| title_full_unstemmed | Dexmedetomidine reduces myocardial ischemia-reperfusion injury in young mice through MIF/AMPK/GLUT4 axis |
| title_short | Dexmedetomidine reduces myocardial ischemia-reperfusion injury in young mice through MIF/AMPK/GLUT4 axis |
| title_sort | dexmedetomidine reduces myocardial ischemia reperfusion injury in young mice through mif ampk glut4 axis |
| topic | Dexmedetomidine (Dex) MIF/AMPK/GLUT4 axis Heart ischemia-reperfusion injury |
| url | https://doi.org/10.1186/s12871-022-01825-z |
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