β2-肾上腺素能受体激动剂福莫特罗能减轻大鼠心肌在实验应激诱导的心脏损伤中的坏死和凋亡。

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Natalia V. Naryzhnaya, Sergey V. Logvinov, Boris K. Kurbatov, Ivan A. Derkachev, Liliia R. Mustafina, Aleksandr S. Gorbunov, Maria A. Sirotina, Mikhail Kilin, Svetlana V. Gusakova, Leonid N. Maslov
{"title":"β2-肾上腺素能受体激动剂福莫特罗能减轻大鼠心肌在实验应激诱导的心脏损伤中的坏死和凋亡。","authors":"Natalia V. Naryzhnaya,&nbsp;Sergey V. Logvinov,&nbsp;Boris K. Kurbatov,&nbsp;Ivan A. Derkachev,&nbsp;Liliia R. Mustafina,&nbsp;Aleksandr S. Gorbunov,&nbsp;Maria A. Sirotina,&nbsp;Mikhail Kilin,&nbsp;Svetlana V. Gusakova,&nbsp;Leonid N. Maslov","doi":"10.1111/fcp.13026","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Currently, there is no effective therapy for takotsubo syndrome (stress-induced cardiac injury in humans) in the clinics. It has previously been shown that β<sub>2</sub>-adrenergic receptor (β<sub>2</sub>-AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome.</p>\n </section>\n \n <section>\n \n <h3> Objectives</h3>\n \n <p>The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress-induced cardiomyopathy.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Stress-induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6 hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase-MB, syndecan-1, and thrombomodulin after 24 hours of stress. Administration of β<sub>2</sub>-AR agonist formoterol (50 μg/kg) four times during 24-hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL-positive cardiomyocytes, serum creatine kinase-MB, syndecan-1, and thrombomodulin levels.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress-induced cardiac injury can be mitigated by activation of the β<sub>2</sub>-AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.</p>\n </section>\n </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 6","pages":"1116-1130"},"PeriodicalIF":2.1000,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The β2-adrenergic receptor agonist formoterol attenuates necrosis and apoptosis in the rat myocardium under experimental stress-induced cardiac injury\",\"authors\":\"Natalia V. Naryzhnaya,&nbsp;Sergey V. Logvinov,&nbsp;Boris K. Kurbatov,&nbsp;Ivan A. Derkachev,&nbsp;Liliia R. Mustafina,&nbsp;Aleksandr S. Gorbunov,&nbsp;Maria A. Sirotina,&nbsp;Mikhail Kilin,&nbsp;Svetlana V. Gusakova,&nbsp;Leonid N. Maslov\",\"doi\":\"10.1111/fcp.13026\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Currently, there is no effective therapy for takotsubo syndrome (stress-induced cardiac injury in humans) in the clinics. It has previously been shown that β<sub>2</sub>-adrenergic receptor (β<sub>2</sub>-AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Objectives</h3>\\n \\n <p>The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress-induced cardiomyopathy.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Stress-induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6 hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase-MB, syndecan-1, and thrombomodulin after 24 hours of stress. Administration of β<sub>2</sub>-AR agonist formoterol (50 μg/kg) four times during 24-hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL-positive cardiomyocytes, serum creatine kinase-MB, syndecan-1, and thrombomodulin levels.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress-induced cardiac injury can be mitigated by activation of the β<sub>2</sub>-AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.</p>\\n </section>\\n </div>\",\"PeriodicalId\":12657,\"journal\":{\"name\":\"Fundamental & Clinical Pharmacology\",\"volume\":\"38 6\",\"pages\":\"1116-1130\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-07-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Fundamental & Clinical Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/fcp.13026\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fundamental & Clinical Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/fcp.13026","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

摘要

背景:目前,临床上还没有治疗拓扑综合征(应激诱发的人类心脏损伤)的有效疗法。之前有研究表明,β2-肾上腺素能受体(β2-AR)激动剂福莫特罗能减轻实验性拓扑综合征的心肌细胞损伤:本研究旨在探讨福莫特罗是否能预防应激诱导的心肌病中心肌细胞和内皮细胞的凋亡和坏死:方法:将大鼠固定2、6和24小时,诱发应激性心肌损伤:结果:应激大鼠的心肌显示出收缩力下降和心肌细胞损伤的组织学表现:核分裂、心肌细胞和内皮细胞的核周水肿以及微循环障碍随着应激时间的延长而加剧。此外,在应激开始 6 小时后检测到内皮细胞凋亡,并在 24 小时后达到高峰。心肌细胞的凋亡仅在应激暴露 24 小时后才显著增加。这些形态学改变与应激 24 小时后血清肌酸激酶-MB、辛迪加-1 和血栓调节蛋白水平的升高有关。在24小时应激暴露期间,给予β2-AR激动剂福莫特罗(50 μg/kg)四次,可改善心肌肌力,降低组织学特征的严重程度,减少TUNEL阳性心肌细胞的数量,降低血清肌酸激酶-MB、辛迪卡-1和血栓调节蛋白的水平:目前的数据表明,在应激诱导的心脏损伤中,心肌细胞的凋亡和坏死以及内皮细胞的坏死可通过激活β2-AR得到缓解。然而,福莫特罗并不能完全消除应激下的心肌细胞凋亡、组织学改变或内皮损伤标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The β2-adrenergic receptor agonist formoterol attenuates necrosis and apoptosis in the rat myocardium under experimental stress-induced cardiac injury

Background

Currently, there is no effective therapy for takotsubo syndrome (stress-induced cardiac injury in humans) in the clinics. It has previously been shown that β2-adrenergic receptor (β2-AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome.

Objectives

The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress-induced cardiomyopathy.

Methods

Stress-induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours.

Results

The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6 hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase-MB, syndecan-1, and thrombomodulin after 24 hours of stress. Administration of β2-AR agonist formoterol (50 μg/kg) four times during 24-hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL-positive cardiomyocytes, serum creatine kinase-MB, syndecan-1, and thrombomodulin levels.

Conclusion

Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress-induced cardiac injury can be mitigated by activation of the β2-AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信