Hydrogen alleviates myocardial infarction by impeding apoptosis via ROS-mediated mitochondrial endogenous pathway.

Abstract

Background: Acute myocardial infarction (AMI) is a deadly cardiovascular disease with no effective solution except for percutaneous coronary intervention and coronary artery bypass grafting. Inflammation and apoptosis of the injured myocardium after revascularization seriously affect the prognosis. Hydrogen possesses anti-inflammatory, anti-oxidative, and anti-apoptotic effects and may become a new treatment for AMI. This study explored the specific mechanism by which hydrogen operates during AMI treatment.

Methods: Thirty Sprague-Dawley rats were randomly divided into three groups: control, myocardial infarction (MI), and myocardial infarction + hydrogen (MI+H₂), each containing 10 rats. The MI rat model was established by ligation of the left anterior descending branch. The MI+H₂ group received 2% hydrogen inhalation treatment for 3 h/Bid.

Results: Myocardial infarct size was evaluated using triphenyl tetrazolium chloride staining. Transmission electron microscopy showed reduced mitochondrial damage compared with the MI group. JC-1 staining, which indicates mitochondrial membrane potential, showed a low red/green fluorescence intensity ratio in the MI group compared to that in the control group, indicating mitochondrial membrane potential loss. After hydrogen inhalation, this ratio increased, suggesting partial recovery of membrane potential. In addition, mitochondrial ATP content, mitochondrial complex I, and mitochondrial complex III activity were significantly decreased in the MI group, which was improved after hydrogen administration. Western blotting analysis showed decreased Cyt-c protein levels in the myocardial mitochondria and increased levels in the cytoplasm of MI rats. Following hydrogen inhalation, the levels of ROS, 8-OHdG, and MDA that could represent oxidative stress injury significantly decreased. Besides, the expression of Cyt-C, Bax, cleaved-caspase-9, and cleaved-caspase-3 in MI group significantly increased, while the Bcl-2, TRX2, SOD2 expression decreased. The expression of these proteins in MI+H2 group was improved compared with the MI group.

Conclusion: Overall, hydrogen inhalation reduces myocardial infarct size, improves mitochondrial dysfunction, and modulates the levels of apoptosis-related substances. Importantly, Hydrogen reduces acute myocardial infarction damage by downregulating ROS and upregulating antioxidant proteins.