[Sodium hydrosulfide attenuates myocardial injury through activating thioredoxin system in diabetic rats]

Objective To investigate the effect of exogenous hydrogen sulfide from sodium hydrosulfide (NaHS) on cardiac thioredoxin (Trx) system in diabetic rats. Methods Male Sprague-Dawley rats were randomly divided into a normal group, a diabetic group, and three NaHS (14, 28 and 56 μmol/kg) treatment groups, with 6 rats in each group. Type 1 diabetes was induced in the groups by a single intraperitoneal (i.p.) injection of streptozotocin. At the fifth week after modeling, the NaHS treatment groups were injected (i.p.) with NaHS at the doses of 14, 28 and 56 μmol/kg once a day, respectively. After the treatment for 4 weeks, the fasting blood glucose (FBG) level and ventricular hemodynamic parameters were measured. The changes of myocardial pathomorphology were observed by HE staining. The ultrastructural changes of cardiomyocytes were observed by transmission electron microscopy. The levels of serum lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase MB isozyme (CK-MB) were examined using the kits. Serum interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) were assayed by ELISA. The levels of total antioxidant capacity (T-AOC), lipid peroxide (LPO), and malondialdehyde (MDA) in myocardium were analyzed using the kits. The mRNA expression of heme oxygenase 1 (HO-1) was detected using reverse transcription PCR (RT-PCR). The expression levels of Trx, Trx-interacting protein (TXNIP), and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) in myocardium were measured using Western blotting. Results Compared with the normal group, the left ventricular systolic and diastolic functions were weakened in the diabetic group, and the myocardial morphological structure and ultrastructure were damaged obviously. The FBG, LDH, CK, CK-MB, IL-1β, IL-6, TNF-α, LPO and MDA levels increased, while the T-AOC level decreased. The myocardial Trx protein expression was reduced, while the expressions of HO-1 mRNA, TXNIP and NOX2 proteins were elevated in the diabetic group. Compared with the diabetic group, the left ventricular systolic and diastolic functions, myocardial morphological structure and ultrastructure were improved in the three NaHS treatment groups. The LDH, CK, CK-MB, IL-1β, IL-6, TNF-α, LPO and MDA levels decreased, while T-AOC increased. The myocardial HO-1 mRNA and Trx protein expressions were enhanced, while TXNIP and NOX2 protein expressions were suppressed. Conclusion NaHS treatment attenuates diabetic myocardial injury, and the mechanisms may be associated with the activation of the Trx system, the enhancement of antioxidant capability and the inhibition of inflammatory factor release.