Effects of esmolol on cardiomyocyte apoptosis in septic rats
Objective To investigate the effect of esmolol, a short-acting, highly selective β-blocker, on cardiomyocyte apoptosis in septic rats and its possible mechanism. Methods A total of 63 male Wistar rats were randomly divided into sham operation group (Sham group), sepsis group (CLP group), and esmolol...
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Editorial Office of Journal of Third Military Medical University
2020-07-01
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Series: | Di-san junyi daxue xuebao |
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Online Access: | http://aammt.tmmu.edu.cn/Upload/rhtml/202002145.htm |
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DOAJ |
language |
zho |
format |
Article |
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DOAJ |
author |
SI Fei ZHEN Lingling WANG Yingzhen ZHANG Bei ZHANG Hongbin TENG Jingqian MA Li |
spellingShingle |
SI Fei ZHEN Lingling WANG Yingzhen ZHANG Bei ZHANG Hongbin TENG Jingqian MA Li Effects of esmolol on cardiomyocyte apoptosis in septic rats Di-san junyi daxue xuebao sepsis esmolol bcl-2 bax caspase-3 oxidative stress mitochondria apoptosis |
author_facet |
SI Fei ZHEN Lingling WANG Yingzhen ZHANG Bei ZHANG Hongbin TENG Jingqian MA Li |
author_sort |
SI Fei |
title |
Effects of esmolol on cardiomyocyte apoptosis in septic rats |
title_short |
Effects of esmolol on cardiomyocyte apoptosis in septic rats |
title_full |
Effects of esmolol on cardiomyocyte apoptosis in septic rats |
title_fullStr |
Effects of esmolol on cardiomyocyte apoptosis in septic rats |
title_full_unstemmed |
Effects of esmolol on cardiomyocyte apoptosis in septic rats |
title_sort |
effects of esmolol on cardiomyocyte apoptosis in septic rats |
publisher |
Editorial Office of Journal of Third Military Medical University |
series |
Di-san junyi daxue xuebao |
issn |
1000-5404 |
publishDate |
2020-07-01 |
description |
Objective To investigate the effect of esmolol, a short-acting, highly selective β-blocker, on cardiomyocyte apoptosis in septic rats and its possible mechanism. Methods A total of 63 male Wistar rats were randomly divided into sham operation group (Sham group), sepsis group (CLP group), and esmolol group (ES group). Each group was further divided into 6-, 12-, and 24-hour subgroups. The rats of the Sham group were given sham surgery only, and those of the CLP and ES groups underwent cecal ligation and puncture (CLP) to establish sepsis model. The Sham group and the CLP group were continuously infused with 0.9% sodium chloride solution at a speed of 1 mL/h by micropump for 6 h, while the ES group was continuously infused with 15 mg/kg·h esmolol diluted solution at 1 mL/h for 6 h. Then the rats were sacrificed at 6, 12 and 24 h after successful modeling, and the heart specimens were collected. Serum TNF-α and BNP levels were measured by ELISA. Water soluble tetrazolium (WST-1) method was used to detect SOD activity, and spectrophotometry to determine MDA content in myocardial tissue. The expression levels of Caspase-3, Bcl-2, Bax and other proteins in myocardial tissue were detected by Western blotting. Transmission electron microscopy was performed to observe the morphology and structure of myocardial mitochondria. Results Compared with the levels at the same time points in Sham group, the serum TNF-α and BNP levels, MDA content, and expression levels of apoptotic proteins such as Caspase-3 and Bax were significantly increased in the CLP and ES groups (P < 0.05). Except the level of BNP in ES24h group was not significantly different than that in CLP24h group (P>0.05), ES group had obviously decreased serum TNF-α and BNP levels, MDA content, and expression levels of Caspase-3 and Bax when compared with those in the CLP group at same time points (P < 0.05). The SOD activity and Bcl-2 level were remarkably higher in the CLP and ES groups at the same time points (P < 0.05), and the activity and levels were increased in the ES group than the CLP group at all time points (P < 0.05). Under a transmission electron microscope, myocardial fibers and mitochondria were almost intact in the Sham group at all time points; the damages were the most severe in the CLP group, and the severity was deteriorated gradually with time elapse, while the conditions became alleviated in the ES group at each time point. Conclusion Esmolol partially improves cardiac function in septic rats by inhibiting cardiomyocyte apoptosis. The mechanism may be due to its inhibition in apoptosis initiation factor TNF-α and regulation in the expression of apoptosis-related proteins such as Bcl-2, Bax, and Caspase-3, and reduction of the oxidative stress response as well. It mediates both the accompanying process of apoptosis and an important initiator of apoptosis, and protects the mitochondrial structure of target organelles damaged by apoptosis and oxidative stress. |
topic |
sepsis esmolol bcl-2 bax caspase-3 oxidative stress mitochondria apoptosis |
url |
http://aammt.tmmu.edu.cn/Upload/rhtml/202002145.htm |
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AT sifei effectsofesmololoncardiomyocyteapoptosisinsepticrats AT zhenlingling effectsofesmololoncardiomyocyteapoptosisinsepticrats AT wangyingzhen effectsofesmololoncardiomyocyteapoptosisinsepticrats AT zhangbei effectsofesmololoncardiomyocyteapoptosisinsepticrats AT zhanghongbin effectsofesmololoncardiomyocyteapoptosisinsepticrats AT tengjingqian effectsofesmololoncardiomyocyteapoptosisinsepticrats AT mali effectsofesmololoncardiomyocyteapoptosisinsepticrats |
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doaj-7bb3f7a0fcdc4048847eca053a59eec72021-05-14T00:58:33ZzhoEditorial Office of Journal of Third Military Medical UniversityDi-san junyi daxue xuebao1000-54042020-07-0142131292130010.16016/j.1000-5404.202002145Effects of esmolol on cardiomyocyte apoptosis in septic rats SI Fei0ZHEN Lingling1WANG Yingzhen2ZHANG Bei3ZHANG Hongbin4TENG Jingqian5MA Li6Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu Province, 730030Ward 3 of Department of Critical Care Medicine, Lanzhou University Second Hospital, Lanzhou, Gansu Province, 730030, China Ward 3 of Department of Critical Care Medicine, Lanzhou University Second Hospital, Lanzhou, Gansu Province, 730030, China Ward 3 of Department of Critical Care Medicine, Lanzhou University Second Hospital, Lanzhou, Gansu Province, 730030, China Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu Province, 730030Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu Province, 730030Ward 3 of Department of Critical Care Medicine, Lanzhou University Second Hospital, Lanzhou, Gansu Province, 730030, China Objective To investigate the effect of esmolol, a short-acting, highly selective β-blocker, on cardiomyocyte apoptosis in septic rats and its possible mechanism. Methods A total of 63 male Wistar rats were randomly divided into sham operation group (Sham group), sepsis group (CLP group), and esmolol group (ES group). Each group was further divided into 6-, 12-, and 24-hour subgroups. The rats of the Sham group were given sham surgery only, and those of the CLP and ES groups underwent cecal ligation and puncture (CLP) to establish sepsis model. The Sham group and the CLP group were continuously infused with 0.9% sodium chloride solution at a speed of 1 mL/h by micropump for 6 h, while the ES group was continuously infused with 15 mg/kg·h esmolol diluted solution at 1 mL/h for 6 h. Then the rats were sacrificed at 6, 12 and 24 h after successful modeling, and the heart specimens were collected. Serum TNF-α and BNP levels were measured by ELISA. Water soluble tetrazolium (WST-1) method was used to detect SOD activity, and spectrophotometry to determine MDA content in myocardial tissue. The expression levels of Caspase-3, Bcl-2, Bax and other proteins in myocardial tissue were detected by Western blotting. Transmission electron microscopy was performed to observe the morphology and structure of myocardial mitochondria. Results Compared with the levels at the same time points in Sham group, the serum TNF-α and BNP levels, MDA content, and expression levels of apoptotic proteins such as Caspase-3 and Bax were significantly increased in the CLP and ES groups (P < 0.05). Except the level of BNP in ES24h group was not significantly different than that in CLP24h group (P>0.05), ES group had obviously decreased serum TNF-α and BNP levels, MDA content, and expression levels of Caspase-3 and Bax when compared with those in the CLP group at same time points (P < 0.05). The SOD activity and Bcl-2 level were remarkably higher in the CLP and ES groups at the same time points (P < 0.05), and the activity and levels were increased in the ES group than the CLP group at all time points (P < 0.05). Under a transmission electron microscope, myocardial fibers and mitochondria were almost intact in the Sham group at all time points; the damages were the most severe in the CLP group, and the severity was deteriorated gradually with time elapse, while the conditions became alleviated in the ES group at each time point. Conclusion Esmolol partially improves cardiac function in septic rats by inhibiting cardiomyocyte apoptosis. The mechanism may be due to its inhibition in apoptosis initiation factor TNF-α and regulation in the expression of apoptosis-related proteins such as Bcl-2, Bax, and Caspase-3, and reduction of the oxidative stress response as well. It mediates both the accompanying process of apoptosis and an important initiator of apoptosis, and protects the mitochondrial structure of target organelles damaged by apoptosis and oxidative stress.http://aammt.tmmu.edu.cn/Upload/rhtml/202002145.htmsepsisesmololbcl-2baxcaspase-3oxidative stressmitochondriaapoptosis |