Exogenous Hydrogen Sulphide Ameliorates Diabetic Cardiomyopathy in Rats by Reversing Disordered Calcium-Handling System in Sarcoplasmic Reticulum

ObjectivesHydrogen sulphide (H2S) has been found to be involved in cardiovascular diseases, but the exact mechanism has not been clarified. The purpose of this study was to investigate whether sodium hydrogen sulphide (NaHS), the donor of H2S, can improve diabetic cardiomyopathy by reversing disordered calcium-handling system in sarcoplasmic reticulum (SR).MethodsSprague Dawley rats were injected with streptozotocin (STZ, 60 mg/kg, i.p.) to build diabetic model. Treatment groups included: aminoguanidine group (AG, 100 mg/kg, p.o.) and NaHS group (5 mg/kg per day, s.c.).Key findingsCardiac dysfunction and myocardial hypertrophy were found in diabetic model (DM) group, along with increased ROS levels and upregulated mRNA and protein expressions of NADPH p22(phox), endothelin A receptor (ETA) and protein kinase C epsilon (PKC epsilon). Expressions of calcium-handling proteins in SR including FK506-binding proteins (FKBP12.6), sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) and calsequestrin 2 (CASQ2) were downregulated in DM group, accompanied by elevated concentration of diastolic free calcium in high glucose-incubated cardiomyocytes, indicating of calcium leak. After treated by NaHS, these abnormalities were attenuated significantly.ConclusionsExogenous H2S played a protective role in diabetic cardiomyopathy by inhibiting abnormal calcium-handling system in SR and ET-NADPH oxidase-PKC epsilon pathway.