PDF(Pubmed)
Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：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可促进MIRI的进展。右美托咪定(Dex)可减轻心肌损伤,已知可以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尚不清楚.
目的：评估Dex在MIRI期间线粒体功能障碍中的功能。
方法：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。进行CCK8测定以测试细胞活力，并通过JC-1染色评估线粒体膜电位。此外,通过Co-IP分析探索Sirt3和Prdx3之间的结合关系。此外，蛋白质表达采用蛋白质印迹法检测。
结果：Dex可以消除H/R诱导的H9C2细胞线粒体功能障碍。此外,H/R处理显著抑制了Sirt3的表达,而Dex部分恢复了这一现象。敲除Sirt3或Prdx3可明显降低Dex对H/R诱导的线粒体损伤的保护作用。同时,Sirt3可通过Prdx3的脱乙酰作用增强Prdx3的功能。
结论：发现Dex通过激活Sirt3/Prdx3通路减轻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MIRI治疗的新策略提供新的思路.
目的：评估Dex在MIRI期间线粒体功能障碍中的功能。
方法：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。进行CCK8测定以测试细胞活力，并通过JC-1染色评估线粒体膜电位。此外,通过Co-IP分析探索Sirt3和Prdx3之间的结合关系。此外，蛋白质表达采用蛋白质印迹法检测。
结果：Dex可以消除H/R诱导的H9C2细胞线粒体功能障碍。此外,H/R处理显著抑制了Sirt3的表达,而Dex部分恢复了这一现象。敲除Sirt3或Prdx3可明显降低Dex对H/R诱导的线粒体损伤的保护作用。同时,Sirt3可通过Prdx3的脱乙酰作用增强Prdx3的功能。
结论：发现Dex通过激活Sirt3/Prdx3通路减轻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MIRI治疗的新策略提供新的思路.
