右美托咪定通过激活 Sirt3/Prdx3 通路缓解缺氧/复氧诱导的心肌细胞线粒体功能障碍

IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY
DARU Journal of Pharmaceutical Sciences Pub Date : 2024-06-01 Epub Date: 2024-02-26 DOI:10.1007/s40199-024-00504-3
Qingyun Tan, Wenming Dong, Qingdong Wang, Li Gao
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引用次数: 0

摘要

背景:心肌缺血再灌注损伤(MIRI心肌缺血再灌注损伤(MIRI)严重威胁着人们的健康。心肌细胞线粒体功能障碍会促进心肌缺血再灌注损伤的恶化。右美托咪定(Dex)可减轻心肌损伤,已知可逆转肺损伤中的线粒体功能障碍。然而,Dex 在 MIRI 期间线粒体功能障碍中的功能仍不清楚:评估 Dex 在 MIRI 期间线粒体功能障碍中的功能:为了研究Dex在MIRI中的功能,将H9C2细胞置于缺氧/复氧(H/R)条件下。方法:为研究 Dex 在 MIRI 中的功能,将 H9C2 细胞置于缺氧/复氧(H/R)条件下,用 CCK8 检测细胞活力,并用 JC-1 染色评估线粒体膜电位。此外,还通过 Co-IP 试验探讨了 Sirt3 和 Prdx3 之间的结合关系。此外,还利用 Western 印迹检测了蛋白质的表达:结果:Dex能消除H/R诱导的H9C2细胞线粒体功能障碍。此外,H/R 处理明显抑制了 Sirt3 的表达,而 Dex 则部分恢复了这一现象。敲除 Sirt3 或 Prdx3 会明显降低 Dex 对 H/R 诱导的线粒体损伤的保护作用。同时,Sirt3可通过Prdx3的去乙酰化增强Prdx3的功能:结论:通过激活 Sirt3/Prdx3 通路,Dex 可减轻 H/R 诱导的心肌细胞线粒体功能障碍。因此,这项研究可能为探索治疗 MIRI 的新策略带来新的启示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dexmedetomidine alleviates Hypoxia/reoxygenation-induced mitochondrial dysfunction in cardiomyocytes via activation of Sirt3/Prdx3 pathway.

Background: Myocardial ischemia/reperfusion injury (MIRI) seriously threatens the health of people. The mitochondrial dysfunction in cardiomyocytes can promote the progression of MIRI. Dexmedetomidine (Dex) could alleviate the myocardial injury, which was known to reverse mitochondrial dysfunction in lung injury. However, the function of Dex in mitochondrial dysfunction during MIRI remains unclear.

Objective: To assess the function of Dex in mitochondrial dysfunction during MIRI.

Methods: To investigate the function of Dex in MIRI, H9C2 cells were placed in condition of hypoxia/reoxygenation (H/R). CCK8 assay was performed to test the cell viability, and the mitochondrial membrane potential was evaluated by JC-1 staining. In addition, the binding relationship between Sirt3 and Prdx3 was explored by Co-IP assay. Furthermore, the protein expressions were examined using western blot.

Results: Dex could abolish H/R-induced mitochondrial dysfunction in H9C2 cells. In addition, H/R treatment significantly inhibited the expression of Sirt3, while Dex partially restored this phenomenon. Knockdown of Sirt3 or Prdx3 obviously reduced the protective effect of Dex on H/R-induced mitochondrial injury. Meanwhile, Sirt3 could enhance the function of Prdx3 via deacetylation of Prdx3.

Conclusion: Dex was found to attenuate H/R-induced mitochondrial dysfunction in cardiomyocytes via activation of Sirt3/Prdx3 pathway. Thus, this study might shed new lights on exploring new strategies for the treatment of MIRI.

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来源期刊
DARU Journal of Pharmaceutical Sciences
DARU Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-
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期刊介绍: DARU Journal of Pharmaceutical Sciences is a peer-reviewed journal published on behalf of Tehran University of Medical Sciences. The journal encompasses all fields of the pharmaceutical sciences and presents timely research on all areas of drug conception, design, manufacture, classification and assessment. The term DARU is derived from the Persian name meaning drug or medicine. This journal is a unique platform to improve the knowledge of researchers and scientists by publishing novel articles including basic and clinical investigations from members of the global scientific community in the forms of original articles, systematic or narrative reviews, meta-analyses, letters, and short communications.
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