Effect of hydrogen sulfide on cardiomyocyte apoptosis in rats with myocardial ischemia-reperfusion injury via the JNK signaling pathway.

OBJECTIVE: The aim of this study was to explore the influence of hydrogen sulfide (H2S) on cardiomyocyte apoptosis in rats with myocardial ischemia-reperfusion injury via the c-Jun N-terminal kinase (JNK) pathway. MATERIALS AND METHODS: A total of 60 normal female Sprague-Dawley (SD) rats aged 38 weeks were divided into 3 groups, including the sham operation group (n=20), ischemia group (n=20) and ischemia + sodium hydrosulfide (NaHS) group (n=20). Subsequently, differences in cardiac function, the morphology of myocardial tissues, protein expression of JNK2, the content of plasma H2S and malondialdehyde (MDA), the activity of superoxide dismutase (SOD), cystathionine-γ-lyase (CSE) and glutathione peroxidase (GSH-Px) were analyzed among rats in all groups. RESULTS: Left ventricular diastolic pressure (LVDP) and maximum rate of pressure rise/fall (± dP/dtmax) were the highest in of rats of the sham operation group and the lowest in the ischemia group. Meanwhile, they were significantly elevated in the ischemia + NaHS group compared with those in the ischemia group (p<0.01). Left ventricular end-diastolic pressure (LVEDP) was the lowest in rats of the sham operation group and the highest in the ischemia group. Similarly, it decreased markedly in the ischemia + NaHS group compared with the ischemia group (p<0.01). Compared with the sham operation group, the perinuclear space in the myocardium was gradually larger, the arrangement of fibers became significantly more disordered, and the damage of mitochondrial cristae and membrane was remarkably more severe in rats in the ischemia group. Compared with the ischemia group, the above-mentioned conditions of rat cardiomyocytes were markedly improved (p<0.01). Meanwhile, the content of H2S and activity of CSE in the cardiomyocytes were altered in rats of the ischemia + NaHS group. Western blotting results indicated that, compared with the sham operation group, both the ischemia group and ischemia + NaHS group showed significantly up-regulated protein expression level of phosphorylated JNK2, with the highest level in the ischemia group. The content of MDA in rat myocardial tissues was markedly higher in the ischemia group than that of the ischemia + NaHS group, with the lowest level in the sham operation group (p<0.01). Additionally, the activity of SOD and GSH-Px in rat myocardial tissues was remarkably worse in the ischemia group than that of the ischemia + NaHS group, and it was the strongest in the sham operation group (p<0.01). CONCLUSIONS: H2S inhibits the activity of the JNK pathway, decreases its phosphorylation level and down-regulates the protein expression level of JNK2, thereby protecting against myocardial ischemia-reperfusion injury.