Affiliation:
1. Institute of Nephrology, Zhong Da Hospital, Medical School of Southeast University, Nanjing, China
2. Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China
Abstract
Abstract
Objectives
Hydrogen 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).
Methods
Sprague 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 findings
Cardiac dysfunction and myocardial hypertrophy were found in diabetic model (DM) group, along with increased ROS levels and upregulated mRNA and protein expressions of NADPH p22phox, endothelin A receptor (ETA) and protein kinase Cε (PKCε). 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.
Conclusions
Exogenous H2S played a protective role in diabetic cardiomyopathy by inhibiting abnormal calcium-handling system in SR and ET-NADPH oxidase-PKCε pathway.
Funder
National Natural Science Foundation of China
Jiangsu Province Natural Science Foundation
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
Cited by
10 articles.
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