Protective effects of exogenous NaHS against sepsis-induced myocardial mitochondrial injury by enhancing the PGC-1α/NRF2 pathway and mitochondrial biosynthesis in mice

American Journal of Translational Research

Dongshi Liang¹ 

[1]The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, P. R. China

关键词: NaHS;    mitochondria biosynthesis;    Nrf2;    PGC-1α;    sepsis;    Tfam;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

This study aimed to examine whether exogenous NaHS can protect myocardial mitochondrial injury from sepsis by enhancing the peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α)/ nuclear factor erythroid-2-related factor 2 (NRF2) pathway and mitochondrial biosynthesis in mice. Animals were divided into sham-operated, sepsis, sepsis + 25 μmol/L NaHS, sepsis + 50 μmol/L NaHS, sepsis + 100 μmol/L NaHS, and sepsis + 200 μmol/L NaHS groups. The myocardial damage was evaluated by hematoxylin and eosin staining for myocardial microstructure and serum cardiac troponin I (cTnI) detection. The myocardial mitochondrial damage was evaluated through transmission electron microscopic observation of mitochondrial microstructure and detection of the degree of myocardial mitochondrial swelling. The adenosine triphosphate (ATP) level was used to appraise the mitochondrial function. The mRNA expression levels of Nrf2, PGC-1α, and Tfam were analyzed to explore the molecular mechanism. Results: In the sepsis group, the structure of myocardial tissue and mitochondria were significantly damaged, the serum cTnI level increased (P < 0.05), the ATP level reduced, the degree of myocardial mitochondrial swelling aggravated, and the mRNA expression levels of Nrf2, PGC-1α, and Tfam increased (P < 0.05). After NaHS treatment, the structure of myocardial tissue and mitochondria improved, the cTnI level reduced, the ATP level increased, the degree of myocardial mitochondrial swelling alleviated, and the mRNA expression level of Nrf2, PGC-1α, and Tfam increased continuously in a dose-dependent manner (P < 0.05). Conclusions: Exogenous NaHS had a protective effect against myocardial mitochondrial injury in sepsis. The mechanism might lie in enhancing the PGC-1α/NRF2 pathway and mitochondrial biosynthesis.

【 授权许可】

CC BY-NC