Effect and mechanism of dimethyl fumarate on septic cardiomyopathy in mice
Objective To investigate the effect and mechanism of dimethyl fumarate (DMF) on septic cardiomyopathy in mice. Methods Thirty C57/BL6J male mice (22~24 g) aged 8~10 weeks were randomly divided into the blank group, the model group and the treatment group (10 mice in each group). The treatment group...
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Editorial Office of Journal of Army Medical University
2022-11-01
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| Series: | 陆军军医大学学报 |
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| Online Access: | http://aammt.tmmu.edu.cn/Upload/rhtml/202205103.htm |
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| author | MIN Weixiang HEN Xuejun MA Dexiang LIU Yu LIU Shuting |
| author_facet | MIN Weixiang HEN Xuejun MA Dexiang LIU Yu LIU Shuting |
| author_sort | MIN Weixiang |
| collection | DOAJ |
| description | Objective To investigate the effect and mechanism of dimethyl fumarate (DMF) on septic cardiomyopathy in mice. Methods Thirty C57/BL6J male mice (22~24 g) aged 8~10 weeks were randomly divided into the blank group, the model group and the treatment group (10 mice in each group). The treatment group had been given intragastric administration of DMF (25 mg/kg) once a day for 7 d, and the other 2 groups were given a gavage of an equal volume of saline. In 1 h after the last time of intragastric administration, half of the mice in the model group and the treatment group were intraperitoneally injected with high-dose (30 mg/kg) lipopolysaccharide (LPS), and half of the mice in the blank group were given an equal volume of saline to observe the survival rate within 72 h. The remaining mice in the model group and treatment group were intraperitoneally injected with LPS (15 mg/kg) and the blank group was given an equal volume of saline. Transthoracic echocardiography was used to evaluate cardiac function within 24 h. The animals were sacrificed and heart and plasma was collected. The levels of CK-MB and LDH in plasma were detected by biochemical analyzer; HE staining was used to observe the myocardial structure; the contents of MDA, GSH and GSSG and the activity of SOD in heart tissues were detected using colorimetric assay; the protein levels of Nrf2 and its downstream target genes in heart were detected by Western blotting. Results The 72 h survival rate of the model group mice was only 20%, while that of the treatment group mice was 80%. Compared with the blank group, the levels of CM-MB and LDH of plasma in the model group increased, and cardiac myocytes were swelling and disordered. LVEF% and FS% both reduced (P < 0.01); the contents of MDA and GSSG surged, but GSH and SOD activity decreased (P < 0.01); the protein levels of Nrf2, HO-1 and SOD2 dropped (P < 0.01). Compared with the model group, the treatment group showed lower levels of myocardial injury markers, improved cardiac function, less damaged myocardial structure and reduced oxidative stress injury, and the protein expression of Nrf2 and its downstream target gene also enhanced (P < 0.01). Conclusion DMF can activate the antioxidant pathway of Nrf2, improve the ability of heart to resist oxidative stress, and play a protective role in septic cardiomyopathy in mice.
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| first_indexed | 2024-04-11T15:22:22Z |
| format | Article |
| id | doaj.art-39be3778443848f781d47f4253a555ff |
| institution | Directory Open Access Journal |
| issn | 2097-0927 |
| language | zho |
| last_indexed | 2024-04-11T15:22:22Z |
| publishDate | 2022-11-01 |
| publisher | Editorial Office of Journal of Army Medical University |
| record_format | Article |
| series | 陆军军医大学学报 |
| spelling | doaj.art-39be3778443848f781d47f4253a555ff2022-12-22T04:16:20ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272022-11-0144222285229010.16016/j.2097-0927.202205103Effect and mechanism of dimethyl fumarate on septic cardiomyopathy in miceMIN Weixiang0HEN Xuejun1MA Dexiang2LIU Yu3 LIU Shuting4Department of Anesthesiology, Sichuan Academy of Medical Sciences · Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, 610072, ChinaDepartment of Anesthesiology, Sichuan Academy of Medical Sciences · Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, 610072, ChinaDepartment of Anesthesiology, Sichuan Academy of Medical Sciences · Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, 610072, ChinaDepartment of Anesthesiology, Sichuan Academy of Medical Sciences · Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, 610072, ChinaDepartment of Anesthesiology, Sichuan Academy of Medical Sciences · Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, 610072, ChinaObjective To investigate the effect and mechanism of dimethyl fumarate (DMF) on septic cardiomyopathy in mice. Methods Thirty C57/BL6J male mice (22~24 g) aged 8~10 weeks were randomly divided into the blank group, the model group and the treatment group (10 mice in each group). The treatment group had been given intragastric administration of DMF (25 mg/kg) once a day for 7 d, and the other 2 groups were given a gavage of an equal volume of saline. In 1 h after the last time of intragastric administration, half of the mice in the model group and the treatment group were intraperitoneally injected with high-dose (30 mg/kg) lipopolysaccharide (LPS), and half of the mice in the blank group were given an equal volume of saline to observe the survival rate within 72 h. The remaining mice in the model group and treatment group were intraperitoneally injected with LPS (15 mg/kg) and the blank group was given an equal volume of saline. Transthoracic echocardiography was used to evaluate cardiac function within 24 h. The animals were sacrificed and heart and plasma was collected. The levels of CK-MB and LDH in plasma were detected by biochemical analyzer; HE staining was used to observe the myocardial structure; the contents of MDA, GSH and GSSG and the activity of SOD in heart tissues were detected using colorimetric assay; the protein levels of Nrf2 and its downstream target genes in heart were detected by Western blotting. Results The 72 h survival rate of the model group mice was only 20%, while that of the treatment group mice was 80%. Compared with the blank group, the levels of CM-MB and LDH of plasma in the model group increased, and cardiac myocytes were swelling and disordered. LVEF% and FS% both reduced (P < 0.01); the contents of MDA and GSSG surged, but GSH and SOD activity decreased (P < 0.01); the protein levels of Nrf2, HO-1 and SOD2 dropped (P < 0.01). Compared with the model group, the treatment group showed lower levels of myocardial injury markers, improved cardiac function, less damaged myocardial structure and reduced oxidative stress injury, and the protein expression of Nrf2 and its downstream target gene also enhanced (P < 0.01). Conclusion DMF can activate the antioxidant pathway of Nrf2, improve the ability of heart to resist oxidative stress, and play a protective role in septic cardiomyopathy in mice. http://aammt.tmmu.edu.cn/Upload/rhtml/202205103.htmseptic cardiomyopathydimethyl fumarateoxidative stressnrf2 |
| spellingShingle | MIN Weixiang HEN Xuejun MA Dexiang LIU Yu LIU Shuting Effect and mechanism of dimethyl fumarate on septic cardiomyopathy in mice 陆军军医大学学报 septic cardiomyopathy dimethyl fumarate oxidative stress nrf2 |
| title | Effect and mechanism of dimethyl fumarate on septic cardiomyopathy in mice |
| title_full | Effect and mechanism of dimethyl fumarate on septic cardiomyopathy in mice |
| title_fullStr | Effect and mechanism of dimethyl fumarate on septic cardiomyopathy in mice |
| title_full_unstemmed | Effect and mechanism of dimethyl fumarate on septic cardiomyopathy in mice |
| title_short | Effect and mechanism of dimethyl fumarate on septic cardiomyopathy in mice |
| title_sort | effect and mechanism of dimethyl fumarate on septic cardiomyopathy in mice |
| topic | septic cardiomyopathy dimethyl fumarate oxidative stress nrf2 |
| url | http://aammt.tmmu.edu.cn/Upload/rhtml/202205103.htm |
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