Knockdown of 11β-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1α pathway

Dongmei Zhu; Lingli Luo; Hanjie Zeng; Zheng Zhang; Min Huang; Suming Zhou

doi:10.7555/JBR.36.20220212

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Dongmei Zhu, Lingli Luo, Hanjie Zeng, Zheng Zhang, Min Huang, Suming Zhou. Knockdown of 11β-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1α pathway[J]. The Journal of Biomedical Research. doi: 10.7555/JBR.36.20220212

Citation:

Dongmei Zhu, Lingli Luo, Hanjie Zeng, Zheng Zhang, Min Huang, Suming Zhou. Knockdown of 11β-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1α pathway[J]. The Journal of Biomedical Research. doi: 10.7555/JBR.36.20220212

Citation:

Dongmei Zhu, Lingli Luo, Hanjie Zeng, Zheng Zhang, Min Huang, Suming Zhou. Knockdown of 11β-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1α pathway[J]. The Journal of Biomedical Research. doi: 10.7555/JBR.36.20220212

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Knockdown of 11β-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1α pathway

doi: 10.7555/JBR.36.20220212

Department of Geriatrics Intensive Care Unit, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China

Funds: This study was supported by grants from the National Natural Science Youth Foundation of China (81501201), the National Natural Science Youth Foundation of Jiangsu Province (BK20151032) to Min Huang, and the project of critical care medicine of the key clinical specialty of Jiangsu Province.

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Corresponding author: Min Huang, Department of Geriatrics Intensive Care Unit, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China. Tel: +86-25-68305051, E-mail: hmdoctor@163.com; Suming Zhou, Department of Geriatrics Intensive Care Unit, the First Affiliated Hospital of Nanjing Medical University,300 Guangzhou Road, Nanjing, Jiangsu 210029, China. Tel: +86-25-68305053, E-mail: zhousmco@aliyun.com
Received: 2022-09-25
Revised: 2022-11-13
Accepted: 2022-11-22

Published: 2022-11-30

Abstract

Abstract

Sepsis-induced myocardial dysfunction is accompanied primarily by severe sepsis, which is associated with high morbidity and mortality. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a reductase, can convert inactive cortisone into metabolically active cortisol. The role of 11β-HSD1 in sepsis-induced myocardial dysfunction remains poorly understood. This study aimed to investigate the effects of 11β-HSD1 in lipopolysaccharide (LPS)-induced mouse model. LPS（10 mg/kg） was administered to wild-type C57BL/6J mice and 11β-HSD1 global knockout mice. Cardiac function was assessed by echocardiography. Transmission electron microscopy and immunohistochemical staining were performed to analyze myocardial mitochondrial injury and record histological changes. The levels of reactive oxygen species and biomarkers of oxidative stress were determined. Polymerase chain reaction analysis, western blot, and immunofluorescent staining were employed to determine the expression of related genes and proteins, respectively. To investigate the role of 11β-HSD1 in sepsis-induced myocardial dysfunction, LPS was used to induce lentivirus-infected neonatal rat ventricular cardiomyocytes. Knockdown of 11β-HSD1 alleviated LPS-induced myocardial mitochondrial injury, oxidative stress, and inflammation, along with improved myocardial function. Furthermore, depletion of 11β-HSD1 promoted the phosphorylation of adenosine 5'‐monophosphate-activated protein kinase, peroxisome proliferator activated receptor gamma coactivator 1α, and silent information regulator 1 protein levels both in vivo and in vitro. The suppression of 11β-HSD1 may be a viable strategy to improve cardiac function against endotoxemia challenges.
- 11β-HSD1,
- LPS,
- sepsis-induced myocardial dysfunction,
- inflammation,
- oxidative stress

CLC number: 542.2, Document code: A
The authors reported no conflict of interests.

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References(26)

References

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