Molecular hydrogen protects against sepsis-induced cardiomyopathy through improving Golgi stress-mediated autophagy, inflammation and apoptosis.

Abstract

Background and purpose: Sepsis-induced cardiomyopathy (SIC) is the primary cause of mortality among people with sepsis. Hydrogen (H₂) has a cardioprotective effect in SIC; however, its specific mechanism remains unclear. We thus explored whether 2% H₂ treatment mitigates SIC through inhibiting Golgi stress and investigated the specific molecular pathways underlying this protective effect.

Experimental approach: Male C57BL/6J mice were subjected to caecal ligation and puncture (CLP) to establish the sepsis model. We measured the 7-day survival rates, cardiac function, myocardial damage enzymes, and myocardial haematoxylin and eosin (H&E) staining to evaluate the 2% H₂ on SIC. Immunofluorescence and electron microscopy were used to observe the morphological changes in the Golgi apparatus (GA). Additionally, a Golgi stress-specific agonist (Brefeldin A) was administered to observe whether the therapeutic effect of inhalation of 2% H₂ could be reversed. Finally, we examined the indicators of autophagy, inflammation and apoptosis to explore how 2% H₂ affects the downstream mechanisms of Golgi stress.

Key results: The 7-day survival rate of mice decreased, cardiac function deteriorated and myocardial damage enzymes increased after CLP. Golgi stress was associated with elevated levels of autophagy, inflammation and apoptosis levels. These levels decreased following the treatment with 2% H₂ inhalation. However, administration of the Golgi stress-specific agonist Brefeldin A reversed the therapeutic effects of 2% H₂.

Conclusions and implications: We found that 2% H₂ exerted a protective effect on SIC, and we determined that its mechanism is related to improving Golgi stress-mediated autophagy, inflammation and apoptosis.