右美托咪定经STAT3/FoxO3a信号转导通路对减轻H9C2心肌细胞缺氧/复氧损伤的作用

doi:10.3760/cma.j.issn.1007-1245.2024.20.001

国际医药卫生导报 ›› 2024, Vol. 30 ›› Issue (20): 3345-3350.DOI: 10.3760/cma.j.issn.1007-1245.2024.20.001

• 病理生理专栏 • 下一篇

右美托咪定经STAT3/FoxO3a信号转导通路对减轻H9C2心肌细胞缺氧/复氧损伤的作用

谭艳华^1,2 江龙² 邹素娟² 侯杰² 王云³ 旷昕³

¹汕头大学医学院，汕头　515041；²南方医科大学附属坪山区人民医院麻醉科，深圳　518118；³南方医科大学附属龙华区人民医院麻醉科，深圳　518109

收稿日期:2024-05-27 出版日期:2024-10-01 发布日期:2024-10-18
通讯作者: 旷昕，Email：kx6924@126.com
基金资助:
国家卫健委医药卫生科技发展研究项目（WKZX2023WX0147）

Dexmedetomidine mitigating hypoxia/reoxygenation injury in H9C2 cardiomyocytes via STAT3/FoxO3a signaling pathway

Tan Yanhua^1,2, Jiang Long², Zou Sujuan², Hou Jie², Wang Yun³, Kuang Xin³

¹Shantou University Medical College, Shantou 515041, China; ²Department of Anesthesiology, Affiliated Pingshan People's Hospital, Southern Medical University, Shenzhen 518118, China; ³Department of Anesthesiology, Affiliated Longhua People's Hospital, Southern Medical University, Shenzhen 518109, China

Received:2024-05-27 Online:2024-10-01 Published:2024-10-18
Contact: Kuang Xin, Email: kx6924@126.com
Supported by:
Medical and Health Science and Technology Development Research Center of the National Health Commission (WKZX2023WX0147)

摘要/Abstract

摘要：

目的　建立大鼠心肌细胞系H9C2细胞缺氧/复氧模型，探究STAT3/ FoxO3a信号转导通路在右美托咪定（Dex）保护心肌缺氧/复氧损伤中的作用。方法　实验时间：2023年7月至11月，地点：香港大学深圳研究院实验室。使用对数生长期的H9C2心肌细胞进行实验，将其分为不同组别：对照组（C组）、缺氧/复氧组（H/R组，缺氧6 h/复氧12 h）、Dex预处理后缺氧/复氧组（D组），以及添加STAT3抑制剂Stattic+Dex预处理后缺氧/复氧组（S组）。通过CCK8试剂盒检测细胞活力，乳酸脱氢酶（LDH）试剂盒检测细胞损伤，丙二醛（MDA）试剂盒检测氧化应激水平，使用蛋白免疫印迹法检测相关蛋白的表达。统计学方法采用单因素方差分析。结果　H/R组H9C2细胞活力、Bcl-2和P62蛋白水平均低于C组，LDH、MDA、Bax、CC-3、LC3和Beclin-1蛋白水平均高于C组（均P<0.05）。Dex组细胞活力、P-STAT3/STAT3比值及Bcl-2、P62、FoxO3a蛋白水平均高于H/R组，LDH、MDA含量及Bax、CC-3、LC3、Beclin-1蛋白水平均低于H/R组（均P<0.05）。STAT3抑制剂可减弱Dex对心肌细胞损伤的保护作用。结论　Dex预处理通过STAT3/FoxO3a信号转导通路，抑制心肌细胞的凋亡和自噬，降低氧化应激水平，减轻缺氧/复氧H9C2细胞损伤，从而减轻心肌缺血再灌注损伤。

关键词:

右美托咪定, 心肌缺血再灌注损伤, STAT3/FoxO3a信号转导通路, 缺氧/复氧, 细胞凋亡

Abstract:

Objective　To establish a hypoxia/reoxygenation (H/R) model using rat cardiomyocyte line H9C2 cells to thoroughly investigate the regulatory role of STAT3/FoxO3a signaling pathway in the protective effects of dexmedetomidine (Dex) against H/R injury in cardiomyocytes. Methods　The study was conducted at Shenzhen Research Institute Laboratory, the University of Hong Kong from July to November 2023.Logarithmically growing H9C2 cardiomyocytes were used for the experiments, and they were divided into different groups: a control group (group C), a hypoxia/reoxygenation group (group H/R, with 6 hours of hypoxia followed by 12 hours of reoxygenation), a Dex pretreatment followed by H/R group (group D), and a STAT3 inhibitor Stattic plus Dex pretreatment followed by H/R group (group S). The cell viability was detected by the CCK8 kit, the degree of cell injury was detected by lactate dehydrogenase (LDH) kit, the oxidative stress level was detected by malondialdehyde (MDA) kit, and the related protein expressions were detected by Western blot. One-way analysis of variance was used. Results　The cell viability, Bcl-2 and P62 protein levels of H9C2 cells in group H/R were lower than those in group C, and the protein levels of LDH, MDA, Bax, CC-3, LC3 and Beclin-1 were higher than those in group C (all P<0.05). The cell viability, P-STAT3 / STAT3 ratio and the protein levels of Bcl-2, P62 and FoxO3 a in group D were higher than those in group H/R, while the contents of LDH and MDA and the protein levels of Bax, CC-3, LC3 and Beclin-1 were lower than those in group H/R (all P<0.05).STAT3 inhibitor can attenuate the protective effect of Dex on myocardial cell injury. Conclusion　Dex preconditioning inhibited the apoptosis and autophagy of cardiomyocytes through STAT3/FoxO3a signal pathway, reduced the oxidative stress level, attenuated the H9C2 cell damage caused by H/R, and thus alleviated myocardial ischemia-reperfusion injury.

Key words:

Dexmedetomidine, Myocardial ischemia-reperfusion injury, STAT3/FoxO3a signal pathway, Hypoxia/reoxygenation, Apoptosis

谭艳华江龙邹素娟侯杰王云旷昕.

右美托咪定经STAT3/FoxO3a信号转导通路对减轻H9C2心肌细胞缺氧/复氧损伤的作用 [J]. 国际医药卫生导报, 2024, 30(20): 3345-3350.

Tan Yanhua, Jiang Long, Zou Sujuan, Hou Jie, Wang Yun, Kuang Xin.

Dexmedetomidine mitigating hypoxia/reoxygenation injury in H9C2 cardiomyocytes via STAT3/FoxO3a signaling pathway [J]. International Medicine and Health Guidance News, 2024, 30(20): 3345-3350.

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右美托咪定经STAT3/FoxO3a信号转导通路对减轻H9C2心肌细胞缺氧/复氧损伤的作用

Dexmedetomidine mitigating hypoxia/reoxygenation injury in H9C2 cardiomyocytes via STAT3/FoxO3a signaling pathway

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