α‑ketoglutarate protects against septic cardiomyopathy by improving mitochondrial mitophagy and fission

作者：Wei Wu, Qiong Ma, Botao Li, Shuang Shi, Gongchang Guan, Jun-Kui Wang, Baoyao Xue, Zhongwei Liu · 发表于：Molecular Medicine Reports · 年份：2025 · DOI：10.3892/mmr.2025.13511 · 被引用次数：9 · 研究领域：Intensive Care Unit Cognitive Disorders、Mitochondrial Function and Pathology、Metabolomics and Mass Spectrometry Studies

Septic cardiomyopathy is a considerable complication in sepsis, which has high mortality rates and an incompletely understood pathophysiology, which hinders the development of effective treatments.α-ketoglutarate (aKG), a component of the tricarboxylic acid cycle, serves a role in cellular metabolic regulation.The present study delved into the therapeutic potential and underlying mechanisms of aKG in ameliorating septic cardiomyopathy.a mouse model of sepsis was generated and treated with aKG via the drinking water.cardiac function was assessed using echocardiography, while the mitochondrial ultrastructure was examined using transmission electron microscopy.additionally, in vitro, rat neonatal ventricular myocytes were treated with lipopolysaccharide (lPS) as a model of sepsis and then treated with aKG.Mitochondrial function was evaluated via aTP production and Seahorse assays.additionally, the levels of reactive oxygen species were determined using dihydroethidium and chloromethyl derivative cM-H 2 dcFda staining, apoptosis was assessed using a Tunel assay, and the expression levels of mitochondria-associated proteins were analyzed by western blotting.Mice subjected to lPS treatment exhibited compromised cardiac function, reflected by elevated levels of atrial natriuretic peptide, B-type natriuretic peptide and β-myosin heavy chain.These mice also exhibited pronounced mitochondrial morphological disruptions and dysfunction in myocardial tissues; treatment with aKG ameliorate...