右美托咪定通过激活 Sirt3/Prdx3 通路减轻心肌细胞缺氧/复氧诱导的线粒体功能障碍。
Dexmedetomidine alleviates Hypoxia/reoxygenation-induced mitochondrial dysfunction in cardiomyocytes via activation of Sirt3/Prdx3 pathway.
机构信息
Department of Anesthesiology, The First Affiliated Hospital of Jiamusi University, No.348, Dexiang Street, Xiangyang District, Jiamusi, 154002, Heilongjiang Province, People's Republic of China.
Department of Anesthesiology, Shenzhen Baoan Hospital of TCM, Shenzhen, 518133, Guangdong Province, People's Republic of China.
出版信息
Daru. 2024 Jun;32(1):189-196. doi: 10.1007/s40199-024-00504-3. Epub 2024 Feb 26.
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.
背景
心肌缺血/再灌注损伤（MIRI）严重威胁人们的健康。心肌细胞中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，已知其可逆转肺损伤中的线粒体功能障碍。然而，Dex 在 MIRI 中线粒体功能障碍中的作用尚不清楚。
目的
评估 Dex 在 MIRI 中线粒体功能障碍中的作用。
方法
为了研究 Dex 在 MIRI 中的作用，将 H9C2 细胞置于缺氧/复氧（H/R）条件下。通过 CCK8 测定法检测细胞活力，并用 JC-1 染色评估线粒体膜电位。此外，通过 Co-IP 测定法探索 Sirt3 和 Prdx3 之间的结合关系。然后，使用 Western blot 检测蛋白表达。
结果
Dex 可消除 H/R 诱导的 H9C2 细胞中线粒体功能障碍。此外，H/R 处理显著抑制了 Sirt3 的表达，而 Dex 部分恢复了这种现象。Sirt3 或 Prdx3 的敲低明显降低了 Dex 对 H/R 诱导的线粒体损伤的保护作用。同时，Sirt3 通过去乙酰化 Prdx3 增强了 Prdx3 的功能。
结论
Dex 通过激活 Sirt3/Prdx3 通路减轻心肌细胞 H/R 诱导的线粒体功能障碍。因此，这项研究可能为探索治疗 MIRI 的新策略提供新的思路。
Zotero 插件